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Synthesis of bacterial cell surface l-glycero-d-manno-heptose (l,d-Hep)- and d-glycero-d-manno-heptose (d,d-Hep)-containing higher carbon sugars is a challenging task. Here, we report a convenient and efficient approach for the synthesis of the l,d-Hep and d,d-Hep building blocks. Using l-lyxose and d-ribose as starting materials, this approach features diastereoselective Mukaiyama-type aldol reactions as the key steps. On the basis of the synthetic l,d-Hep and d,d-Hep building blocks, we achieved the first stereoselective synthesis of the unique α-l,d-Hep-(1→3)-α-d,d-Hep-(1→5)-α-Kdo core trisaccharide of the lipopolysaccharide of Vibrio parahemolyticus O2.

Ginsenoside-Rg1 (G-Rg1), a saponin that is a primary component of ginseng, is effective against inflammatory diseases. The P2X purinoceptor 7 (P2X7) receptor is an ATP-gated ion channel that is predominantly expressed in immune cells and plays a key role in inflammatory processes. We investigated the role of G-Rg1 in sepsis-related cardiac dysfunction and the underlying mechanism involving the regulation of the P2X7 receptor. We detected cell viability, cytotoxicity, cellular reactive oxygen species (ROS) levels, and mitochondrial membrane potential (MMP) with or without G-Rg1 in lipopolysaccharide (LPS)- or hypoxia/reoxygenation (H/R)-induced H9c2 cell models of ischemia/reperfusion injury. We applied cecal ligation and puncture (CLP) to induce a mouse model of sepsis and measured the survival duration and cardiac function of CLP mice. Next, we quantified the ROS level, MMP, respiratory chain complex I-IV enzymatic activity, and mitochondrial fusion in CLP mouse heart tissues. We then investigated the role of G-Rg1 in repairing LPS-induced cell mitochondrial damage, including mitochondrial superoxidation products. The results showed that G-Rg1 inhibited LPS- or H/R-induced cardiomyocyte apoptosis, cytotoxicity, ROS levels, and mitochondrial damage. In addition, G-Rg1 prolonged the survival time of CLP mice. G-Rg1 attenuated LPS-induced superoxide production in the mitochondria of cardiomyocytes and the excessive release of cytochrome c from mitochondria into the cytoplasm. Most importantly, G-Rg1 suppressed LPS-mediated induction of proapoptotic Bax, activated Akt, induced GSK-3β phosphorylation, and balanced mitochondrial calcium levels. Overall, G-Rg1 activates the Akt/GSK-3β pathway through P2X7 receptors to inhibit sepsis-induced cardiac dysfunction and mitochondrial dysfunction.

The present study aimed to investigate the regulatory mechanism of chemokine (C-X-C motif) receptor 4 (CXCR4) on endothelial progenitor cells (EPCs) through the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway under hypoxic conditions. Mononuclear cells were isolated from the bone marrow (BM) of young Sprague-Dawley (SD) rats. Bone marrow-derived endothelial progenitor cells (BM-EPCs) were characterized by using Dil-labeled acetylated low-density lipoprotein (Dil-ac-LDL) and fluorescein isothiocyanate-labeled UEA (FITC-UEA-1). Phenotype identification of BM-EPCs was based on red cytoplasm and green cytomembrane. Flow cytometry was employed to examine the markers CD14, CD34, and KDR. Expression level of the EPC-specific surface marker CD14 was found to be negative, while the expression level of CD34 and KDR was positive. In addition, CXCR4 was stably overexpressed in BM-EPCs after transfection with adenovirus-CXCR4. Cell proliferation, migration and apoptosis abilities were measured through the application of CCK-8, followed by Transwell and flow cytometry assays. The expression level of CXCR4, PI3K and Akt was determined by reverse transcription-quantitative PCR and western blotting assays. Functional experiments demonstrated that hypoxia inhibited BM-EPC proliferation and migration, while accelerating BM-EPC apoptosis. Additionally, CXCR4 was found to promote proliferation and migration, and suppress apoptosis in BM-EPCs with or without hypoxia treatment. Evidence also demonstrated that CXCR4 markedly upregulated the expression levels of PI3K and Akt. Furthermore, PI3K inhibitor (LY294002) and CXCR4 inhibitor (AMD3100) effectively inhibited the proliferation, migration and resistance to apoptosis of CXCR4-mediated BM-EPCs under hypoxic conditions.

Sepsis, a life-threatening systemic syndrome related to inflammatory response, usually accompanied by major organ dysfunctions. The aim of the present study was to elucidate the role by which Shengmai injection (SMI) acts to septic cardiomyopathy. Initially, the induced mice with septic cardiomyopathy were treated with SMI or normal saline (NS) with oe-caspase-3, and HL-1 cells were treated with oe-Beclin-1 and oe-caspase-3 and then cultured with lipopolysaccharide (LPS). Subsequently, we measured the cardiac troponin I (cTnI) level, and expression of mitochondrial autophagy protein (parkin and pink1) and myocardial cell autophagy-related proteins (LC3-II and LC3-I). Additionally, we identified the cleavage of Beclin-1 by caspase-3 and detected the changes of mitochondrial membrane potential, level of reactive oxygen species (ROS), and apoptosis of myocardial cells in myocardial tissues of mice. It has been demonstrated that SMI contributed to the increase of myocardial mitochondrial autophagy, reduction of cTnI level, and elevation of mitochondrial membrane potential in septic cardiomyopathy mice. Both in vitro and in vivo experiments showed that caspase-3 promoted cleavage of Beclin-1 and release of ROS, whereas repressed lipopolysaccharide (LPS)-induced mitochondrial autophagy. Furthermore, the facilitation of myocardial mitochondrial autophagy and protection of myocardial mitochondria by SMI through inhibition of cleavage Beclin-1 by caspase-3 in septic cardiomyopathy mice were also proved by in vivo experiments. Taken together, SMI could protect myocardial mitochondria by promoting myocardial mitochondrial autophagy in septic cardiomyopathy via inhibition of cleavage of Beclin-1 by caspase-3. Our study demonstrates that SMI could represent a novel target for treatment of septic cardiomyopathy.

A gold(i)-promoted α-selective sialylation approach with 5-N,4-O-oxazolidinone-protected sialyl ortho-hexynylbenzoates as donors is described for the stereoselective synthesis of α-sialosides. Iterative couplings of the 'active' sialyl ortho-hexynylbenzoates and the 'latent' sialyl ortho-iodobenzoates provide a new approach for the 'latent-active' synthesis of α-(2 → 9)-linked oligosialic acids that are relevant to N. meningitidis serogroup C capsular polysaccharide.

Background The black soldier fly (Hermetia illucens) has significant economic potential. The larvae can be used in financially viable waste management systems, as they are voracious feeders able to efficiently convert low-quality waste into valuable biomass. However, most studies on H. illucens in recent decades have focused on optimizing their breeding and bioconversion conditions, while information on their biology is limited. Methods About 200 fifth instar well-fed larvae were sacrificed in this work. The liquid chromatography-tandem mass spectrometry and scanning electron microscopy were employed in this study to perform a proteomic and ultrastructural analysis of the peritrophic matrix (PM) of H. illucens larvae. Results A total of 565 proteins were identified in the PM samples of H. illucen, of which 177 proteins were predicted to contain signal peptides, bioinformatics analysis and manual curation determined 88 proteins may be associated with the PM, with functions in digestion, immunity, PM modulation, and others. The ultrastructure of the H. illucens larval PM observed by scanning electron microscopy shows a unique diamond-shaped chitin grid texture. Conclusions It is the first and most comprehensive proteomics research about the PM of H. illucens larvae to date. All the proteins identified in this work has been discussed in details, except several unnamed or uncharacterized proteins, which should not be ignored and need further study. A comparison of the ultrastructure between H. illucens larval PM and those of other insects as observed by SEM indicates that the PM displays diverse textures on an ultra-micro scale and we suscept a unique diamond-shaped chitin grid texture may help H. illucens larval to hold more food. This work deepens our understanding of the molecular architecture and ultrastructure of the H. illucens larval PM.

Synthesis of bacterial cell surface l

Doxorubicin (DOX) is a widely used cytotoxic drug whose application is limited by its severe side effects. Little was known regarding how to offset its side effects. Therefore this study aims to explore the role of miR-200a-3p in DOX-induced cardiotoxicity and its possible mechanism. DOX-induced myocardial injury rat models were established, which were then injected with miR-200a-3p inhibitor (miR-200a-3p suppression) to observe the effects of miR-200a-3p on cell proliferation, and apoptosis. Heart function and weights of rat models were also measured. Cardiomyocytes were induced by DOX, in which PEG3 knockdown or corresponding plasmids were transfected to assess the possible effect of PEG3 on cell activity. Dual luciferase reporter assay was applied to verify the binding of PEG3 with miR-200a-3p. Elevated levels of lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB) and left ventricular end-diastolic pressure (LVEDP), as well as suppressed left ventricular systolic pressure (LVSP) and ± dp/dt max were showed in myocardial injury rat models. DOX induced myocardial injury and increased miR-200a-3p expression levels. miR-200a-3p inhibitor could partially attenuate DOX-induced cardiotoxicity in rat models, while PEG3 could regulate myocardial injury in DOX-treated cell models. miR-200a-3p, by targeting PEG3 through SIRT1/NF-κB signal pathway, regulated cell proliferation, inflammation and apoptosis of myocardiocytes. The results in current study demonstrated that miR-200a-3p regulates cell proliferation and apoptosis of cardiomyocytes by targeting PEG3 through SIRT1/NF-κB signal pathway. This result may provide a potential clue for the treatment of DOX-induced cardiotoxicity.

Resveratrol (RES) protects myocardial cells from hypoxia/reoxygenation (H/R)-caused injury. However, the mechanism of this effect has not been clarified. Thus, in this study, we aimed to determine whether RES attenuates H/R-induced cell necroptosis by inhibiting the tumor necrosis factor-alpha (TNF-α)/receptor-interacting protein kinase 1 (RIP1)/RIP3/mixed-lineage kinase domain-like (MLKL) signaling pathway. Rat myocardial ischemia/reperfusion (I/R) models and H/R-injured cell models were constructed. Our study showed that myocardial H/R injury significantly increased the levels of TNF-α, RIP1, RIP3, and p-MLKL/MLKL by western blot analysis. Cell viability assay and 4,6-dianmidino-2-phenylindole (DAPI)-propidium iodide staining showed that the cell viability was decreased, and necroptosis was increased after myocardial H/R injury. The expressions of TNF-α, RIP1, RIP3, and p-MLKL/MLKL in H/R myocardial cells treated with different concentrations of RES were significantly downregulated. In addition, we also found that the cell viability was increased and necroptosis was decreased in dose-dependent manners when H/R-injured cells were treated with RES. In addition, the enhanced effect of TNF-α on necroptosis in myocardial H/R-injured cells was improved by RES, and the effect of RES was confirmed in vivo in I/R rats. This study also showed that RES suppresses necroptosis in H9c2 cells, which may occur through the inhibition of the TNF-α/RIP1/RIP3/MLKL signaling pathway. Our data suggest that necroptosis is a promising therapeutic target and may be a promising therapeutic target for the treatment of myocardial I/R injury.

Atopic dermatitis (AD) is the most common chronic inflammatory skin disease and is driven by strong type 2 immune responses. Lactobacillus helveticus NS8 (NS8), a probiotic strain isolated from Mongolian koumiss, has anti-inflammatory activities. Here, we evaluated the therapeutic potential of NS8 on AD-like skin lesions by using SKH-1 hairless mice that underwent three cycles of epicutaneous sensitization (EC) with ovalbumin (OVA). NS8 (5 × 108 CFU/day) was orally administered to mice from 2 weeks before the first sensitization until the end of the study. NS8 attenuated the symptoms and pathological changes in the skin of AD mice. For example, NS8 reduced epidermal and dermal thickening and significantly restrained the infiltration of mast cells, eosinophils, and CD4+ T cells into the dermis. By analysing the Th1/Th2 cytokines produced in skin lesions, we found that NS8 significantly suppressed the expression of IL-4, IL-5, and IL-13 (P

Chitosan (CS) has limited capacity for Ca(II)-adsorption abilities. Here, glutaraldehyde cross-linked chitosan (GLA-CTS) and maltose chitosan (MAL-CTS) were obtained by physical and chemical modifications to improve the adsorption of Ca2+. By comparing the adsorption kinetics and isotherm, the adsorption capabilities of GLA-CTS and MAL-CTS reached 112.27 ± 2.63 and 240.38 ± 31.88 mg/g in the presence of concentrations of 3000 mg/L Ca2+, which were about 2.1 and 4.6 times than CS. The structures of the resulting calcified complexes were profiled by SEM, XPS, FT-IR, and 13C NMR. Unlike the folds and spherical particles observed in CS-Ca(II) and GLA-CTS-Ca(II), the surface morphology of MAL-CTS-Ca(II) presented as flat-membrane-structures. In XPS assays, the peaks of Ca in GLA-CTS-Ca(II) and MAL-CTS-Ca(II) were significantly higher than that of CS-Ca(II), and the percentages of Ca atoms on the surfaces were 1.67 and 1.95 times higher respectively. Structural analyses were indicated from the FT-IR and 13C NMR results, the –NH2, –NHCOCH3 and –OH groups were all involved in the adsorption to Ca2+, and the worked groups were changed when calcium contents increased. Accordingly, possible structures of Ca(II)-complexes and the adsorption mechanisms were initially proposed. These two chitosan derivatives with evidently improved Ca(II)-adsorption are favorable for developing applications based chitosan.

To investigate the construction of the histological section datasets in the basal ganglia of digitized human brain to provide a reference for the meso-level histological data acquisition. A fresh adult brain from a cadaver with no neurological disease was selected, and tissue blocks of the basal ganglia in the right hemisphere was extracted using the visualization method, followed by pretreatments including gradient dehydrating, gelatin-embedding and setting of calibration points. And then the tissue blocks was cryosectioned into 60-μm-thick coronal sections and the sectional images were captured simultaneously by a digital camera at a fixed position. Two series of sections (one section out of ten) were Nissl-stained with Toluidine blue and immunostained with the calbindin D-28K, respectively. Stained sections were digitized by a high resolution scanner. After alignment and registration, contours of nuclei and different nucleic function divisions in the digital images of stained sections were identified, and then were segmented and labeled using software exploited by ourselves. Datasets of one set of registrated serial sectional images and two sets of registrated histochemically stained images in basal ganglia area were obtained, which provide a histological reference for the neurosurgery and diagnostic imaging. a systematic method of cutting, slicing, staining, data acquisition and image registration of large tissue blocks was established, providing a reference for histological data acquisition on the digital human. Anat Rec, 300:1011-1021, 2017. © 2016 Wiley Periodicals, Inc.

Sepsis, a life-threatening systemic syndrome related to inflammatory response, usually accompanied by major organ dysfunctions. The aim of the present study was to elucidate the role by which Shengmai injection (SMI) acts to septic cardiomyopathy.Initially, the induced mice with septic cardiomyopathy were treated with SMI or normal saline (NS) with oe-caspase-3, and HL-1 cells were treated with oe-Beclin-1 and oe-caspase-3 and then cultured with lipopolysaccharide (LPS). Subsequently, we measured the cardiac troponin I (cTnI) level, and expression of mitochondrial autophagy protein (parkin and pink1) and myocardial cell autophagy-related proteins (LC3-II and LC3-I). Additionally, we identified the cleavage of Beclin-1 by caspase-3 and detected the changes of mitochondrial membrane potential, level of reactive oxygen species (ROS), and apoptosis of myocardial cells in myocardial tissues of mice.It has been demonstrated that SMI contributed to the increase of myocardial mitochondrial autophagy, reduction of cTnI level, and elevation of mitochondrial membrane potential in septic cardiomyopathy mice. Both in vitro and in vivo experiments showed that caspase-3 promoted cleavage of Beclin-1 and release of ROS, whereas repressed lipopolysaccharide (LPS)-induced mitochondrial autophagy. Furthermore, the facilitation of myocardial mitochondrial autophagy and protection of myocardial mitochondria by SMI through inhibition of cleavage Beclin-1 by caspase-3 in septic cardiomyopathy mice were also proved by in vivo experiments.Taken together, SMI could protect myocardial mitochondria by promoting myocardial mitochondrial autophagy in septic cardiomyopathy via inhibition of cleavage of Beclin-1 by caspase-3. Our study demonstrates that SMI could represent a novel target for treatment of septic cardiomyopathy.

It is now widely accepted that Hexapoda emerged from Crustacea. Compared to the ubiquitous calcified exoskeleton in crustaceans, a mineralized cuticle in insects is extremely rare. Catecholamine-driven protein cross-links play a leading role in the sclerotization of insect cuticle. In this study, mineralization was discovered in the pupal cuticle of Bactrocera dorsalis (Diptera: Tephritidae), a common pest of fruit farms. We mainly profiled the features of mineralized pupal cuticles from B. dorsalis and its white mutant B. dorsaliswh and unmineralized cuticle from Musca domestica using high-resolution field emission scanning electron microscopy (SEM) and transmission electron microscopy (TEM) combined with structural analysis involving infrared (IR) spectroscopy, X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), and synchrotron X-ray absorption near-edge structure (XANES) spectroscopy. We also compared the thermodynamic and mechanical properties of different pupal cuticles. The results showed that the pupal cuticles of B. dorsalis contain a phase of stable amorphous calcium phosphate (ACP) with a high level of magnesium, which is mainly distributed in the exocuticle and assists in the formation of a graded, stiffened cuticle structure. Unexpectedly, this ACP possesses a very low Ca/P ratio and has a composition similar to that of CaHPO4·2H2O. The degree of mineralization in the pupal cuticle of B. dorsaliswh (approximately 22 wt%) is significantly greater than that of wild-type B. dorsalis (approximately 12 wt%), which indicates that there may be a connection between the biomineralization and tyrosine-mediated tanning pathways. These findings provide new evidence for the mineralization of the insect cuticle, which may shed new light on the evolutionary mechanism underlying the divergence of cuticle sclerotization between insects and crustaceans.

Myocardial ischemia/reperfusion (IR) injury is one of the most prevalent cardiovascular diseases, known for its high mortality and morbidity worldwide. Based on pre-existing evidence, LGALS3 has been found to be closely associated with cardiac diseases. Hence, the objective of our study is to explore the potential function of KCNQ1OT1/microRNA-204-5p (miR-204-5p)/ LGALS3 axis on myocardial IR injury and the underlying mechanism. A myocardial IR injury mouse model was established in vivo and an in vitro cardiomyocyte model was induced by hypoxia/Reoxygenation exposure. Next, gain- and loss-of-function experiments were employed in order to measure the viability and apoptosis of cardiomyocytes and the area of ischemic infarct by CCK-8, TUNEL staining and Evans blue/TTC double staining. LGALS3 was found to be highly expressed in myocardial IR injury. The downregulation of LGALS3 resulted in the alleviation of myocardial IR injury in mouse models. In addition, KCNQ1OT1 could promote the LGALS3 expression by binding to miR-204-5p, which led to aggravated myocardial IR injury. In conclusion, KCNQ1OT1 binds to miR-204-5p to exacerbate myocardial IR injury in mice through the up-regulation of LGALS3, providing a novel insight for myocardial IR injury treatment.

Background and aim Chronic inflammation is a major contributor to the initiation and progression of cancers. Lactobacillus helveticus NS8, which was originally separated from fermented koumiss, exhibited anti-inflammatory functions in our prior studies. In this study, NS8 was investigated for its potential to prevent colitis-associated colorectal cancer (CAC). Methods The protective effects of NS8 against CAC was explored by employing the azoxymethane plus dextran sodium sulfate-induced carcinogenesis mouse model. The prevalences of T cells expressing specific inflammatory cytokines were measured by flow cytometry at the early stage of CAC. Inflammatory modulation by NS8 was also tested in the Caco2-Raw264.7 cell co-culture system. The alternations in the intestinal microbiota following the health-inflammation-cancer sequence were analyzed by 16S rDNA sequencing. Results Oral intake of NS8 lactobacilli clearly reduced tumor number and the degree of hyperplasia. The increased proliferation of enterocytes at the early stage of CAC was significantly suppressed by NS8, while the level of apoptosis was elevated. The anticancer effects of NS8 were associated with its anti-colitis outcomes before tumor formation. NS8 significantly suppressed the activation of NF-κB and upregulated the anti-inflammatory cytokine IL-10. Further analysis revealed the marked downregulation of IL-17-producing T cells by NS8. Furthermore, NS8 modulated intestinal dysbiosis by promoting beneficial commensal microbes while suppressing cancer-associated microbes. Notably, Bacteroides acidifaciens was the most sensitive commensal bacteria to NS8 intervention. Conclusion These results provide insight into the protective effects of L. helveticus NS8 against colorectal cancer.

microRNAs (miRs) are essential in the development of heart failure. The aim of this study is to investigate the effect of microRNA-330 (miR-330) on left ventricular remodeling via the TGF-β1/Smad3 signaling pathway by targeting the sex-determining region Y (SRY) in mice with myocardial ischemia-reperfusion injury (MIRI). Differentially expressed gene (DEG) in myocardial ischemia-reperfusion (IR) was screened out and the miR that targeted the DEG was also predicted and verified. A model of MIRI was established to detect the expression of miR-330, SRY, transforming growth factor-β (TGF-β1), and Sekelsky mothers against dpp3 (Smad3). To further investigate the role of miR-330 in MIRI with the involvement of SRY and TGF-β1/Smad3 signaling pathway, the modeled mice were treated with different mimic, inhibitor, or small interfering RNA (siRNA) to observe the changes of the related gene expression, as well as the myocardial infarction size and volume of myocardial collagen. SRY was screened out and verified as a target gene of miR-330. The MIRI mice showed enlarged myocardial infarction size, increased volume of myocardial collagen, increased expression of miR-330, TGF-β1 and Smad3, while decreased the expression of SRY. The MIRI mice treated with miR-330 inhibitor showed decreased myocardial infarction size, the volume of myocardial collagen, and expression of TGF-β1 and Smad3 but promoted expression of SRY. Our findings demonstrated that downregulated miR-330 could suppress left ventricular remodeling to inhibit the activation of the TGF-β1/Smad3 signaling pathway via negatively targeting of SRY in mice with MIRI. This can be a potential target in the strategy to attenuate patient suffering.

Background Bone mesenchymal stem cell (BMSC) therapy has modest success in ischemic heart disease but has been limited by poor survival in diseased microenvironments. Cellular repressor of E1A-stimulated genes (CREG) can prevent BMSCs from apoptosis in vitro ; however, the effects of CREG-modified BMSCs on ischemic heart disease and the related mechanism remain undefined. Therefore, we designed to study the cardioprotective effects of CREG overexpression in BMSCs ( CREG BMSCs) after transplantation into infarcted heart of rats. Methods In vivo studies, 50μl PBS or 1.5×10 6 Norm BMSCs, GFP BMSCs or CREG BMSCs were implanted intramyocardially in myocardial infarction rat models. 3 or 14days later, cardiac function, fibrosis, apoptosis and angiogenesis were analyzed by echocardiography, masson, western blot and immunofluorescence staining, respectively. ELISA, western blot and matrigel assay were used in vitro to detect vascular endothelial growth factor (VEGF) secretion, signaling molecule expression, and angiogenic tube formation. Results In vivo , prolonged cardiac function (14d LVEF: 50.87±0.94%; LVFS: 23.41±1.12%), decreased fibrosis (14d Fibrotic area: 27.37±1.03%) and apoptosis and increased angiogenesis were observed in CREG BMSCs, compared with other groups. In vivo and in vitro , VEGF secretion from CREG BMSCs was markedly enhanced. In vitro , angiogenic tube formation in CREG BMSC supernatants significantly increased. Moreover, CREG activated hypoxia-inducible factor-1α (HIF-1α), but not HIF-1β. Knockdown of HIF-1α with siRNA decreased VEGF secretion and angiogenic tube formation. Notably, CREG did not influence HIF-1α mRNA synthesis but inhibited the expression of Von Hippel–Lindau (VHL), a key protein that regulates HIF-1α degradation. Conclusions The CREG BMSC transplantation, directly or indirectly, may promote VEGF's anti-apoptosis and angiogenesis via the inhibition of VHL-mediated HIF-1α degradation, consequently protecting against myocardial infarction.

Atopic dermatitis (AD) is the most common chronic inflammatory skin disease and is driven by strong type 2 immune responses. Lactobacillus helveticus NS8 (NS8), a probiotic strain isolated from Mongolian koumiss, has anti-inflammatory activities. Here, we evaluated the therapeutic potential of NS8 on AD-like skin lesions by using SKH-1 hairless mice that underwent three cycles of epicutaneous sensitization (EC) with ovalbumin (OVA). NS8 (5 × 10(8) CFU/day) was orally administered to mice from 2 weeks before the first sensitization until the end of the study. NS8 attenuated the symptoms and pathological changes in the skin of AD mice. For example, NS8 reduced epidermal and dermal thickening and significantly restrained the infiltration of mast cells, eosinophils, and CD4(+) T cells into the dermis. By analysing the Th1/Th2 cytokines produced in skin lesions, we found that NS8 significantly suppressed the expression of IL-4, IL-5, and IL-13 (P

Background. Until now, there has been no ideal embolization agent for hemorrhage in interventional treatment. In this study, the thrombin was encapsulated in alginate calcium microsphere using electrostatic droplet technique to produce new embolization agent: thrombin loaded alginate calcium microspheres (TACMs).Objectives. The present work was to evaluate the biocompatibility and hemostatic efficiency of TACMs.Methods.Cell cytotoxicity, hemolysis, and superselective embolization of dog liver arteries were performed to investigate the biocompatibility of TACMs. To clarify the embolic effect of TACMs mixed thrombus in vivo, hepatic artery injury animal model of 6 beagles was established and transcatheter artery embolization for bleeding was performed.Results. Coculture with VECs revealed the noncytotoxicity of TACMs, and the hemolysis experiment was negligible. Moreover, the histological study of TACMs in liver blood vessel showed signs of a slight inflammatory reaction. The results of transcatheter application of TACMs mixed thrombus for bleeding showed that the blood flow was shut down completely after the TACMs mixed thrombus was delivered and the postprocedural survival rate of animal models at 12 weeks was 100%.Conclusions. With their good biocompatibility and superior hemostatic efficiency, TACMs might be a promising new hemostatic agent with a wide range of potential applications.

The syntheses and characterization of the glycoluril, 1,5-diamino-3,7-dioxo-2,4,6,8-tetraazabicyclo[3.3.0]-octane (1), and a novel 3D infinite structure coordination polymer, [Na2(H2O)4(ITDO)2]n (ITDO = 2H-imidazo-[4,5-e]-as-1,2,4-triazine-2,7-dihydro-3,6-dione) (2) are described. Their crystal structures both belong to monoclinic space group P21/n. In the structure of 2 sodium is hexacoordinated by two types of both aqua ligands (monodentate and end-on bridge) and ITDO ligand (end-on bridge and end-to-end bridge). The ITDO ligand, which may have a potential application in anti-cancer therapy, is reported for the first time. Thermal analysis of 1 shows only one endothermic peak at 184.5 °C. Thermal analysis of 2 indicates two endothermic processes and three main successive exothermic processes occurred as shown in the DSC curve. The first endothermic peak temperature is 143.4 °C and the first exothermic peak temperature is 461.7 °C, which exhibits good thermal stability. Density functional theory calculations were performed for 2, which indicate that 2 is a kind of ionic complex and combined by electrostatic interaction. Moreover, the ITDO ligand is an active group in the chemical reactions of 2.

Aims Here, we investigated the preventive properties of the supernatant of Lactobacillus helveticus NS8-fermented milk (NS8-FS) against UV light-induced skin oxidative damage and hyperpigmentation. Methods and Results NS8-FS exhibited significant radical scavenging activity in tests with ABST+ and DPPH scavenging methods, and as well strongly inhibited 3-morpholinosydnonimine (Sin-1) induced ROS generation in HaCat keratinocytes. Unexpectedly, NS8-FS was found to inhibit melanin production in B16F10 melanoma cells, and to exhibit inhibitory effects both to the enzymatic activity of tyrosinase and the expression of proteins required for melanin synthesis. In SKH-1 hairless mice, topical application of NS8-FS alleviated UVB-induced skin photodamage, including the improvement of the appearance of epidermal thickness, transepidennal water loss, and lipid peroxidation levels. In the tanning guinea pig model, the whitening effect of NS8-FS was demonstrated using Masson-Fontana staining and tyrosinase staining. Furthermore, NS8-FS was shown to stimulate the nuclear translocation and activation of the Nrf2 protein, along with recovery of antioxidant enzyme activities. Conclusion NS8-FS exhibits the protective capacities against UV light-induced skin oxidative damage and hyperpigmentation. Significance and Impact of the Study Our findings indicate the potential of cell-free fermented products of lactic acid bacteria in topical photoprotection. This article is protected by copyright. All rights reserved.

Transcatheter arterial embolization (TAE) is the best non-laparotomy choice for solid visceral organs rupture and bleeding nowadays. In our previous study, a new biodegradable macromolecule material thrombin-loaded alginate-calcium microsphere (TACM) was prepared and its characteristics were investigated preliminarily. In this study, we further investigated the biocompatibility of TACMs, as well as physical characteristic, application method and effect of TACMs with thrombus (embolic agent). The in vivo results attested that TACMs were non-irritating and non-genotoxic with desired biocompatibility, although brought about a slight and temporary inflammation. Application research showed that the function of thrombin was inhibited by common contrast agents, and it was impracticable to add contrast agents in TACMs with thrombus for tracing under X-rays in TAE. Then, a novel delivery method was developed. In addition, stress resistance test indicated that the TACMs with thrombus was significantly stronger than single autologous thrombus, the optimized ratio of TACMs to whole blood was 2:3 for forming mixed thrombus. Finally, large animal experiment revealed that the novel embolic agent - TACMs mixed thrombus was effective and safe in treating hemorrhage of solid abdominal viscera by TAE.

To investigate the construction of the histological section datasets in the basal ganglia of digitized human brain to provide a reference for the meso-level histological data acquisition. A fresh adult brain from a cadaver with no neurological disease was selected, and tissue blocks of the basal ganglia in the right hemisphere was extracted using the visualization method, followed by pretreatments including gradient dehydrating, gelatin-embedding and setting of calibration points. And then the tissue blocks was cryosectioned into 60-μm-thick coronal sections and the sectional images were captured simultaneously by a digital camera at a fixed position. Two series of sections (one section out of ten) were Nissl-stained with Toluidine blue and immunostained with the calbindin D-28K, respectively. Stained sections were digitized by a high resolution scanner. After alignment and registration, contours of nuclei and different nucleic function divisions in the digital images of stained sections were identified, and then were segmented and labeled using software exploited by ourselves. Datasets of one set of registrated serial sectional images and two sets of registrated histochemically stained images in basal ganglia area were obtained, which provide a histological reference for the neurosurgery and diagnostic imaging. a systematic method of cutting, slicing, staining, data acquisition and image registration of large tissue blocks was established, providing a reference for histological data acquisition on the digital human. Anat Rec, 300:1011-1021, 2017. © 2016 Wiley Periodicals, Inc.

Table S1. Lewis acid-base characteristics of the bacterial cell surfaces. Adhesion to chloroform (electron acceptor) and ethyl acetate (electron donor) was also tested to assess the Lewis acid-base characteristics of the bacterial cell surfaces. All the strains didnâ t show significant difference between the affinity to chloroform and to ethyl acetate. (PDF 46 kb)

Figure S1. Autoaggregation percentage of L. helveticus NS8 in 5 hours. The sedimentation rate of strains was measured over a period of 5 h under identical conditions. NS8 isolate exhibited the highest cell autoaggregation. The autoaggregating phenotype of NS8 was so strong that over half bacterium have formed a precipitate in 1 h, while other bacterial suspensions showed constant turbidity with little precipitate. (PDF 159 kb)

To date, transcatheter arterial embolization (TAE) has become a standard treatment to control intracavitary bleeding as an alternative to surgery. Due to excellent biocompatibility and no residual in vivo, biodegradable materials are preferred in TAE. However, gelfoam is the only commercially available biodegradable embolic material used to treat blunt trauma of solid abdominal viscera until now, and controversial on its stability and reliability never stopped in the past five decades. In this study, a new biodegradable macromolecule material (thrombin-loaded alginate-calcium microspheres, TACMs) was prepared using electrostatic droplet techniques and a special method was developed for hemostatic embolization. Thrombin was successfully loaded into microspheres with high encapsulation efficiency and drug loading capacity. A burst release of TACMs was observed at early stage and sustained release later on, with the activity of thrombin preserved well. The strength of TACMs mixed thrombus, which was used as embolic agent, increased in a dose-dependent manner after TACMs were added. In addition, the TACMs were verified to be of no cytotoxicity and systemic toxicity, and biodegradable in vivo. Finally, the results of preliminary applications revealed that the TACMs could serve as an effective and promising embolic material for blunt trauma and hemorrhage of solid abdominal viscera.

Introduction Endothelium dysfunction plays a critical role in atherosclerosis. MicroRNAs are endogenous non-coding RNAs that suppress gene expression by binding to the 3’ untranslated regions of target genes. MiR-495 can regulate the proliferation and apoptosis of cancer cells, however, the roles of miR-495 in endothelial cells (ECs) remain unclear. Therefore, this study aims to investigate the roles and mechanisms of miR-495 on ECs proliferation and apoptosis. Materials and Methods MiR-495 and CCL2 expressions were examined using quantitative RT-PCR, ELISA assay and western blot. Bioinformatics analysis and luciferase reporter assay were used to examine the regulatory relationship between miR-495 and CCL2. CCK8 assay, BrdU incorporation assay and flow cytometry were used to analyze the roles of miR-495 and CCL2 on the proliferation of human umbilical vein endothelial cells (HUVECs). The effects of miR-495 and CCL2 on HUVECs apoptosis were examined by tunnel staining and western blot. Results MiR-495 was down-regulated in patients with coronary artery disease compared with healthy controls. CCL2 was a novel target gene of miR-495. MiR-495 significantly promoted HUVECs proliferation by altering cell cycle distribution, and it also inhibited HUVECs apoptosis by affecting the expression of cleaved caspase 3. Effects of miR-495 on HUVECs proliferation and apoptosis were significantly reversed by overexpression of CCL2. Conclusions MiR-495 could affect HUVECs proliferation and apoptosis by directly targeting CCL2. This is the first report to disclose the roles and mechanisms of miR-495 on HUVECs proliferation and apoptosis, which may provide a theoretical basis for clarifying the mechanisms of atherosclerosis.

The lack of medical facilities causes delayed diagnosis and treatment of coronary heart disease in remote mountainous area and/or at disaster site. The miniature mobile cardiac catheterization laboratory was developed to be an intervention platform for coronary heart disease diagnosis and treatment by our team. Pre-clinical research indicated that the miniature mobile cardiac catheterization laboratory performed well in the rescue of critical cardiovascular diseases, even ST-segment elevation myocardial infarction. The present study aimed to evaluate the clinical safety and timeliness of the miniature mobile cardiac catheterization laboratory for emergent coronary interventional diagnosis and treatment.X-ray radiation safety and disinfection efficacy in the miniature mobile cardiac catheterization laboratory were tested during working status. Coronary angiography and/or percutaneous coronary intervention were performed in remote mountainous areas on patients who were first diagnosed as having coronary heart disease by senior interventional cardiologists. The percutaneous coronary intervention procedures and results from patients in the miniature mobile cardiac catheterization laboratory were compared with patients who were treated in the hospital catheter lab.The X-ray radiation dosages in the miniature mobile cardiac catheterization laboratory were 39.55 µGy/s, 247.4 µGy/h, 90.3 µGy/h and 39.4 µGy/h which were corresponded to 0 m, 1 m, 2 m and 3 m away from the tube central of the medium C-arm. And the radiation dosages used in the miniature mobile cardiac catheterization laboratory were less than the corresponding positions in the hospital catheter lab. The numbers of bacteria colonies in the miniature mobile cardiac catheterization laboratory in different environments range from (60 ± 8) cfu/m(3) to (120 ± 10) cfu/m(3) and met the demands of percutaneous coronary intervention. A total of 17 patients who received angiography in the miniature mobile cardiac catheterization laboratory, eight received percutaneous coronary intervention. The operations were all successfully accomplished without intraoperative and postoperative complications. The average angiography and percutaneous coronary intervention times were 35 ± 9 minutes and 55 ± 11 minutes, respectively. There was no significant difference in immediate percutaneous coronary intervention results between the miniature mobile cardiac catheterization laboratory and the catheter lab.It is safe and feasible to carry out clinical interventional diagnosis and treatment in the miniature mobile cardiac catheterization laboratory as determined by this research. The miniature mobile cardiac catheterization laboratory may be considered a newly developed diagnosis and treatment platform for rescuing coronary heart disease patients in remote mountainous areas and/or at disaster sites.

Objective To study the possibility of Chinese visible human (CVH) head datasets as brain atlas for locating the subthalamic nucleus (STN) before deep brain stimulation (DBS) surgery. Methods Optimal head axial and coronal 3.0T, T2-weighted magnetic resonance images (MRI) of 30 patients were obtained. Cross-sectional head images of four CVH head datasets were chosen to establish an average CVH model. All MRI sequences were registered to the CVH model via fiducials in X-, Y-, and Z-direction, respectively, within the same stereotactic space. The correlations between red nucleus (RN) and fiducials, the accuracy of MRI-to-CVH registration, and the coordinate value differences of RN gravity center between MRI and CVH were tested. Results The mean gravity center coordinate values and ranges of STN in CVH were measured; The X coordinate value of RN positively correlates with the most anterior point of putamen(PU-A), the lateral edges of putamens (PU-L), and width of the third ventricle, negatively correlated with the patients’ age; The minimal mean errors were when no fiducials were used when locating RN between the MRI and the CVH average model; There were no significant differences of RN in X- and Y-direction between MRI sequences and CVH. Conclusion CVH head datasets can be used as brain atlas for Chinese STN localization. Moreover, average coordinate values of the gravity center and the ranges of STN in CVH can be considered as references for locating STN.