Rapid Hemostatic Biomaterial from a Natural Bath Sponge Skeleton

Uncontrolled bleeding is the main cause of mortality from trauma. Collagen has been developed as an important hemostatic material due to its platelet affinity function. A bath sponge skeleton is rich in collagen, also known as spongin. To understand the hemostatic effect of spongin, spongin materials, SX, SFM and SR were prepared from the bath sponge Spongia officinalis, and hemostatic experiments were performed. The SX, SFM and SR were significantly better than the positive control, type I collagen, in shortening the whole blood clotting time in vitro and hemostasis upon rat tail amputation. In a hemostatic experiment of rabbit common carotid artery injury, the hemostatic time and 3 h survival rate of the SFM group were 3.00 ± 1.53 min and 100%, respectively, which are significantly better than those of the commercial hemostat CELOX-A (10.33 ± 1.37 min and 67%, respectively). Additionally, the SFM showed good coagulation effects in platelet-deficient blood and defibrinated blood, while also showing good biocompatibility. Through a variety of tests, we speculated that the hemostatic activity of the SFM is mainly caused by its hyperabsorbency, high affinity to platelets and high effective concentration. Overall, the SFM and spongin derivates could be potential hemostatic agents for uncontrolled bleeding and hemorrhagic diseases caused by deficiency or dysfunction of coagulation factors.     

The Chemically Highly Diversified Metabolites from the Red Sea Marine Sponge Spongia sp.

A polyoxygenated and halogenated labdane, spongianol (1); a polyoxygenated steroid, 3β,5α,9α-trihydroxy-24S-ethylcholest-7-en-6-one (2); a rare seven-membered lactone B ring, (22E,24S)-ergosta-7,22-dien-3β,5α-diol-6,5-olide (3); and an α,β-unsaturated fatty acid, (Z)-3-methyl-9-oxodec-2-enoic acid (4) as well as five known compounds, 10-hydroxykahukuene B (5), pacifenol (6), dysidamide (7), 7,7,7-trichloro-3-hydroxy-2,2,6-trimethyl-4-(4,4,4-trichloro-3-methyl-1-oxobu-tylamino)-heptanoic acid methyl ester (8), and the primary metabolite 2’-deoxynucleoside thymidine (9), have been isolated from the Red Sea sponge Spongia sp. The stereoisomer of 3 was discovered in Ganoderma resinaceum, and metabolites 5 and 6, isolated previously from red algae, were characterized unprecedentedly in the sponge. Compounds 7 and 8 have not been found before in the genus Spongia. Compounds 1–9 were also assayed for cytotoxicity as well as antibacterial and anti-inflammatory activities.     

Design and Preclinical Evaluation of Chitosan/Kaolin Nanocomposites with Enhanced Hemostatic Efficiency

In the current study, hemostatic compositions including a combination of chitosan and kaolin have been developed. Chitosan is a marine polysaccharide derived from chitins, a structural component in the shells of crustaceans. Both chitosan and kaolin have the ability to mediate a quick and efficient hemostatic effect following immediate application to injury sites, and thus they have been widely exploited in manufacturing of hemostatic composites. By combining more than one hemostatic agent (i.e., chitosan and kaolin) that act via more than one mechanism, and by utilizing different nanotechnology-based approaches to enhance the surface areas, the capability of the dressing to control bleeding was improved, in terms of amount of blood loss and time to hemostasis. The nanotechnology-based approaches utilized to enhance the effective surface area of the hemostatic agents included the use of Pluronic nanoparticles, and deposition of chitosan micro- and nano-fibers onto the carrier. The developed composites effectively controlled bleeding and significantly improved hemostasis and survival rates in two animal models, rats and rabbits, compared to conventional dressings and QuikClot^® Combat Gauze. The composites were well-tolerated as demonstrated by their in vivo biocompatibility and absence of clinical and biochemical changes in the laboratory animals after application of the dressings.     

Solomonsterol A,a Marine Pregnane-X-Receptor Agonist,Attenuates Inflammation and Immune Dysfunction in a Mouse Model of Arthritis

In the present study we provide evidence that solomonsterol A, a selective pregnane X receptor (PXR) agonist isolated from the marine sponge Theonella swinhoei, exerts anti-inflammatory activity and attenuates systemic inflammation and immune dysfunction in a mouse model of rheumatoid arthritis. Solomonsterol A was effective in protecting against the development of arthritis induced by injecting transgenic mice harboring a humanized PXR, with anti-collagen antibodies (CAIA) with beneficial effects on joint histopathology and local inflammatory response reducing the expression of inflammatory markers (TNFα, IFNγ and IL-17 and chemokines MIP1α and RANTES) in draining lymph nodes. Solomonsterol A rescued mice from systemic inflammation were assessed by measuring arthritis score, CRP and cytokines in the blood. In summary, the present study provides a molecular basis for the regulation of systemic local and systemic immunity by PXR agonists.     

茶多酚对动物血清血脂和载脂蛋白水平的影响和抗氧化作用

采用Transansio全自动生化分析仪、自动冲洗旋转式血液流变仪及Chrono -log4 0 0血小板聚集仪分别测定各试验组动物血脂、血粘度、凝血时间、血小板聚集率脂质过氧化物及载脂蛋白水平的作用。结果 2 0 0mg kg-1·d-1茶多酚处理具有明显降低高脂血症小白鼠的血清TC、TG、LDL -C、apoB10 0 ,升高HDL -C (P     

Relative and Absolute Stereochemistry of Diacarperoxides: Antimalarial Norditerpene Endoperoxides from Marine Sponge Diacarnus megaspinorhabdosa

Five new norditerpene endoperoxides, named diacarperoxides H–L (1–5), and a new norditerpene diol, called diacardiol B (6), were isolated from the South China Sea sponge, Diacarnus megaspinorhabdosa. Their structures, including conformations and absolute configurations, were determined by using spectroscopic analyses, computational approaches and chemical degradation. Diacarperoxides H–J (1–3) showed some interesting stereochemical issues, as well as antimalarial activity.     

ESI FTICR-MS Analysis of Larvae from the Marine Sponge Luffariella variabilis

The viviparous Great Barrier Reef sponge Luffariella variabilis (Poléjaeff 1884) contains a range of secondary metabolites, including manoalide (1) and manoalide monoacetate (3). ESI (+) FTICR-MS accurate mass determination has, for the first time, been used to detected the presence of 3 only in an organic extract of a single L. variabilis larva showing that the parentally produced 3 is sequestered in the larva. As 3 has previously been shown to have antibacterial and quorum sensing inhibition activity, and readily converts to 1, which also exhibits similar activity, it may provide a chemical defence against predation and microbial attack.     

Isolation of Araguspongine M,a New Stereoisomer of an Araguspongine/Xestospongin alkaloid,and Dopamine from the Marine Sponge Neopetrosia exigua Collected in Palau

A new stereoisomer of an araguspongine/xestospongin alkaloid, named araguspongine M (1), has been isolated together with 12 known compounds, araguspongines B (2) and D (3), dopamine, three galactosyl diacylglycerols, 24-methyl cholesterol, 5,6-dihydrocholesterol, β-sitosterol, and three 5α,8α-epidioxy sterols (11–13), from the marine sponge Neopetrosia exigua (formerly Xestospongia exigua) collected in Palau. The structure of 1 was assigned on the basis of its spectral data analysis. This is the first report on the isolation of dopamine from a marine sponge. This compound may be produced by an endosymbiotic Synechococcus-like cyanobacterium. Compounds 1–3 and 11–13 showed cytotoxicity against HL-60 at IC₅₀’s of 5.5, 5.5, 5.9, 22.4, 9.5, and 9.6 μM, respectively. The possible biosynthesis origin of the isolated metabolites is discussed.     

Amylopectin Fine Structure and Rice Starch Paste Breakdown

Ten rice starches with a fairly narrow range of amylose content, but wide variation in RVA pasting curves, were selected to study a possible relationship between amylopectin fine structure and RVA paste viscosity parameters. Amylopectin fine structure was found to significantly correlate with paste breakdown. Proportion of long chains of amylopectin (FrI) was negatively correlated (r=0·84, p<0·01) and proportion of short chains of amylopectin (FrIII) was positive correlated (r=0·89, p<0·001) with paste breakdown. The findings imply that amylopectin fine structure relates to the extent of breakdown of swollen granules and the viscosity after gelatinised starch granule structure is disrupted. The results suggest the possibility that lines can be selected with high proportion of amylopectin long chains for reduced paste breakdown.     

Targeted Isolation of a Cytotoxic Cyclic Hexadepsipeptide from the Mesophotic Zone Sponge-Associated Fungus Cymostachys sp. NBUF082

LC-MS/MS-based molecular networking facilitated the targeted isolation of a new cyclic hexadepsipeptide, cymodepsipeptide (1), and two known analogues, RF–2691A (2) and RF–2691B (3), from the fungus Cymostachys sp. NBUF082 that was derived from a mesophotic zone Aaptos sponge collected near Apo Island. The constitution and configuration of 1 was elucidated through 1D and 2D NMR-spectroscopy, high resolution mass-spectrometry, and chemical degradations including Marfey’s analysis and chiral HPLC. It was observed that 1 was moderately cytotoxic against CCRF-CEM human acute lymphocytic leukemia cells in vitro with the IC₅₀ value of 9.2 ± 1.1 μM.     

Antibacterial Cyclic Tripeptides from Antarctica-Sponge-Derived Fungus Aspergillus insulicola HDN151418

Three new aspochracin-type cyclic tripeptides, sclerotiotides M–O (1–3), together with three known analogues, sclerotiotide L (4), sclerotiotide F (5), and sclerotiotide B (6), were obtained from the ethyl acetate extract of the fungus Aspergillus insulicola HDN151418, which was isolated from an unidentified Antarctica sponge. Spectroscopic and chemical approaches were used to elucidate their structures. The absolute configuration of the side chain in compound 4 was elucidated for the first time. Compounds 1 and 2 showed broad antimicrobial activity against a panel of pathogenic strains, including Bacillus cereus, Proteus species, Mycobacterium phlei, Bacillus subtilis, Vibrio parahemolyticus, Edwardsiella tarda, MRCNS, and MRSA, with MIC values ranging from 1.56 to 25.0 µM.     

Localization and Characterization of Ferritin in Demospongiae: A Possible Role on Spiculogenesis

Iron, as inorganic ion or as oxide, is widely used by biological systems in a myriad of biological functions (e.g., enzymatic, gene activation and/or regulation). In particular, marine organisms containing silica structures—diatoms and sponges—grow preferentially in the presence of iron. Using primary sponge cell culture from S. domuncula–primmorphs—as an in vitro model to study the Demospongiae spiculogenesis, we found the presence of agglomerates 50 nm in diameter exclusively inside sponge specialized cells called sclerocytes. A clear phase/material separation is observed between the agglomerates and the initial stages of intracellular spicule formation. STEM-HRTEM-EDX analysis of the agglomerates (30–100 nm) showed that they are composed of pseudohexagonal nanoparticles between 5 and 15 nm in size, displaying lattice parameters corresponding to hematite (Fe₂O₃) and mixed iron oxide phases typically attributed to ferritin. Further analysis, using western blotting, inductively coupled plasma mass spectrometry (ICP-MS), sequence alignment analysis, immunostaining and magnetic resonance imaging (MRI), of mature spicule filaments confirm the presence of ferritin within these organic structures. We suggest that S. domuncula can be classified as a dual biomineralizating organism, i.e., within the same cellular structure two distinct biomineralizing processes can occur as a result of the same cellular/metabolic function, spiculogenesis.     

碟脉灵注射液对急性血瘀模型大鼠血液流变学的影响

采用大鼠皮下注射0.1%肾上腺素加冰水中浸泡5min复制急性血瘀模型,观察碟脉灵注射液对急性血瘀模型大鼠血液流变学的影响。结果表明,碟脉灵注射液2.5、5、10ml/kg可使急性血瘀模型大鼠全血黏度、血浆黏度、血浆纤维蛋白原浓度、血沉、红细胞压积、红细胞电泳时间、红细胞聚集指数及红细胞刚性指数均明显降低。提示其对急性血瘀模型大鼠血液流变学的异常变化有明显改善作用,这有利于防止急性心肌梗死及脑梗死时的高黏状态,预防血栓形成。     

Natural and Semisynthetic Analogues of Manadoperoxide B Reveal New Structural Requirements for Trypanocidal Activity

Chemical analysis of the Indonesian sponge Plakortis cfr. lita afforded two new analogues of the potent trypanocidal agent manadoperoxide B (1), namely 12-isomanadoperoxide B (2) and manadoperoxidic acid B (3). These compounds were isolated along with a new short chain dicarboxylate monoester (4), bearing some interesting relationships with the polyketide endoperoxides found in this sponge. Some semi-synthetic analogues of manadoperoxide B (6–8) were prepared and evaluated for antitrypanosomal activity and cytotoxicity. These studies revealed crucial structure–activity relationships that should be taken into account in the design of optimized and simplified endoperoxyketal trypanocidal agents.     

Water soluble carboxymethylcellulose fibers derived from alkalization-etherification of viscose fibers

Carboxymethylcellulose (CMC) fibers have been successfully prepared from viscose fibers through the process of alkalization-etherification. Parameters including reaction temperature, mass ratio of NaOH to the viscose fibers, and mass ratio of the viscose fibers to ethanol are studied. The degree of substitution (DS) and the inherent viscosity of the CMC fibers are determined. The CMC fibers are characterized by using Fourier transform infrared spectroscopy (FT-IR), ¹H-nuclear magnetic resonance spectroscopy (¹H-NMR), scanning electron microscopy (SEM), and the X-ray diffraction (XRD). The analysis demonstrates that under the experimental conditions where the reaction temperature is 40 °C, mass ratio of NaOH to the viscose fibers is 2.0, and mass ratio of the viscose fibers to ethanol is 1:15, the obtained CMC fibers possess an appropriate DS, better water-solubility, and lower degree of etching, thus they can be used as absorbable hemostatic fibers.     

Polyketides and Meroterpenes from the Marine-Derived Fungi Aspergillus unguis 158SC-067 and A. flocculosus 01NT-1.1.5 and Their Cytotoxic and Antioxidant Activities

Ten secondary metabolites, including a new grifolin analog, grifolin B (1); a new homovalencic acid derivative, 12-hydroxyhomovalencic acid (7); and a compound isolated from a natural source for the first time (9), along with seven known compounds, grifolin (2), averantin (3), 7-chloroaverantin (4), 1′-O-methylaverantin (5), 7-hydroxy-2-(2-hydroxypropyl)-5-pentylchromone (6), homovalencic acid (8), and bekeleylactone E (10), were isolated from two fungal strains. The structures of 1–10 were identified by detailed analysis and comparison of their spectroscopic data with literature values. Compounds 9 and 10 showed moderate cytotoxic activity against a panel of cancer cell lines (PC-3, HCT-15, MDA-MB-231, ACHN, NCI-H23, NUGC-3), with the GI₅₀ values ranging from 1.1 µM to 3.6 µM, whereas 1 displayed a weak 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity without cytotoxicity against all tested cell lines.     

Study of the effect of hydrothermal process conditions on pasta quality

The effect of hydrothermal treatment on the pasting, hydration properties and colour quality of commercial fresh pasta were studied following an Instantaneous Controlled Pressure Drop treatment. This hydrothermal procedure involves a physical modification at high temperature (<144 °C) and restricted moisture content (<30%) during a very short time (15–40 s) followed by a rapid pressure drop to a vacuum (50 mbar). Two process variables (steam pressure level and processing time) were investigated using response surface methodology. Steam pressure level had the greatest effect on hydration and pasting parameters. Increased pressure resulted in elevation of mass ratio between cooked and uncooked pasta (W_i/W₀)_{100 °C} and reduction of for all treated pasta. The optimum cooking time of untreated pasta was 7 min (W/W₀=2.4), whereas for the same ratio it was less than 1 min for pasta treated at pressures ranging between 2.5 and 3.5 bar. The viscosity at 10 min (V₁₀) increased linearly when the pressure level increased. V₁₀ was 146 cP for untreated pasta whereas it reached 2659 cP for pasta treated at 3.9 bar (144 °C) for 25 s. The cold paste viscosity and setback viscosity decreased when the pressure varied from 1 to 3.9 bar.     

Structure-Activity Relationship and in Vivo Anti-Tumor Evaluations of Dictyoceratin-A and -C,Hypoxia-Selective Growth Inhibitors from Marine Sponge

Oral dictyoceratin-C (1) and A (2), hypoxia-selective growth inhibitors, showed potent in vivo antitumor effects in mice subcutaneously inoculated with sarcoma S180 cells. Structurally modified analogs were synthesized to assess the structure–activity relationship of the natural compounds 1 and 2 isolated from a marine sponge. Biological evaluation of these analogs showed that the exo-olefin and hydroxyl and methyl ester moieties were important for the hypoxia-selective growth inhibitory activities of 1 and 2. Thus far, only substitution of the methyl ester with propargyl amide in 1 was found to be effective for the synthesis of probe molecules for target identification.     

Production,Characterization and Biocompatibility of Marine Collagen Matrices from an Alternative and Sustainable Source: The Sea Urchin Paracentrotus lividus

Collagen has become a key-molecule in cell culture studies and in the tissue engineering field. Industrially, the principal sources of collagen are calf skin and bones which, however, could be associated to risks of serious disease transmission. In fact, collagen derived from alternative and riskless sources is required, and marine organisms are among the safest and recently exploited ones. Sea urchins possess a circular area of soft tissue surrounding the mouth, the peristomial membrane (PM), mainly composed by mammalian-like collagen. The PM of the edible sea urchin Paracentrotus lividus therefore represents a potential unexploited collagen source, easily obtainable as a food industry waste product. Our results demonstrate that it is possible to extract native collagen fibrils from the PM and produce suitable substrates for in vitro system. The obtained matrices appear as a homogeneous fibrillar network (mean fibril diameter 30–400 nm and mesh < 2 μm) and display remarkable mechanical properties in term of stiffness (146 ± 48 MPa) and viscosity (60.98 ± 52.07 GPa·s). In vitro tests with horse pbMSC show a good biocompatibility in terms of overall cell growth. The obtained results indicate that the sea urchin P. lividus can be a valuable low-cost collagen source for mechanically resistant biomedical devices.     

Fabrication of oxidized sodium carboxymethylcellulose from viscose fibers and their viscosity behaviors

The oxidized sodium carboxymethylcellulose (O-CMC) fibers have been successfully synthesized via the oxidation-etherification method. Subsequently, the O-CMC fibers are characterized by Fourier transform infrared (FT-IR), ¹³C nuclear magnetic resonance (¹³C-NMR) and X-ray diffraction (XRD). In addition, the viscosity behaviors of the O-CMC aqueous solution have been investigated at five temperatures (25, 30, 40, 50 and 60 °C), six concentrations (30, 35, 40, 45, 50 and 60 kg/m³) and four shear rates (6, 12, 30 and 60 rpm). The results show that the viscosity of the O-CMC aqueous solution increases with increasing concentrations and decreases with increasing temperature. The viscosity of the O-CMC aqueous solution is found to exhibit a dilatant behavior. The dissolution rate in water of the O-CMC fibers is faster than that of the carboxymethylcellulose (CMC) fibers. It could be used as novel absorbable hemostatic fibers in surgery.