Analysis of the topological motifs of the cellular structure of the tri-spine horseshoe crab (Tachypleus tridentatus) and its associated mechanical properties.

Topological motifs in pore architecture can profoundly influence the structural properties of that architecture, such as its mass, porosity, modulus, strength, and surface permeability. Taking the irregular cellular structure of the tri-spine horseshoe crab as a research model, we present a new approach to the quantitative description and analysis of structure-property-function relationships. We employ a robust skeletonization method to construct a curve-skeleton that relies on high-resolution 3D tomographic data. The topological motifs and mechanical properties of the long-range cellular structure were investigated using the Grasshopper plugin and uniaxial compression test to identify the variation gradient. Finite element analysis was conducted for the sub-volumes to obtain the variation in effective modulus along the three principal directions. The results show that the branch length and node distribution density varied from the tip to the base of the sharp corner. These node types formed a low-connectivity network, in which the node types 3-N and 4-N tended to follow the motifs of ideal planar triangle and tetrahedral configurations, respectively, with the highest proportion of inter-branch angles in the angle ranges of 115-120° and 105-110°. In addition, mapping the mechanical gradients to topological properties indicated that narrower profiles with a given branch length gradient, preferred branch orientation, and network connectedness degree are the main factors that affect the mechanical properties. These factors suggest significant potential for designing a controllable, irregularly cellular structure in terms of both morphology and function.

Structural characterization and regulation of the mechanical properties of the carapace cuticle in tri-spine horseshoe crab (Tachypleus tridentatus).

Horseshoe crab (order Xiphosura) has a large and thick carapace that has evolved as a protective tool to defend against predators and resist impacts from surf-zone turbulence. The naturally occurring spatial variation in the mechanical properties of the carapace cuticle need to be investigated to understand their regulatory mechanism and the underlying design strategies. In this work, we used a combination of high-resolution optical microscopy, scanning electron microscopy, (SEM) and energy-dispersive X-ray spectroscopy (EDS) to evaluate the multiscale microstructure and elemental composition of the cuticle of tri-spine horseshoe crab (Tachypleus tridentatus). The moduli, ultimate strengths, and failure strains of the three individual layers and the entire cuticle were systematically characterized in both the dry and hydrated states. The failure behaviors and energy absorption of the cuticle involved stress stiffening, toughness mechanism and environmental adaptation were analyzed qualitatively and quantitatively and then correlated with the morphological features in different cuticle regions. The mechanical properties are primarily influenced by the endocuticle thickness ratio; a higher thickness ratio corresponds to more stacking of the vertical lamellae, leading to a lower modulus, weaker strength, and greater elongation of the endocuticle. Radial energy is absorbed primarily by the endocuticle, with the energy absorbed in the radial direction being nearly twice that absorbed in the circumferential direction. This is attributed to the larger failure strain and relatively small decrease in the stress plateau in the radial direction. The findings provide a deeper understanding of how nature modulates the cuticle's mechanical properties and inspiration for developing high-performance synthetic composites.

Long-term oral Asperosaponin VI attenuates cardiac dysfunction, myocardial fibrosis in a rat model of chronic myocardial infarction.

The aim of the study was to determine the effects of Asperosaponin VI (ASA VI), a triterpene saponin isolated from Dipsacus asper Wall, on chronic myocardial infarction (MI) and possible mechanisms in rats. MI was induced by permanent ligation of the left coronary artery. Twenty-four hours after MI, the rats were administered the extract by gavage (once a day). Six weeks after MI/sham surgery, cardiac dysfunction, infarct size (IS), cardiac fibrosis, hydroxyproline concentration, the oxidative stress parameter and inflammation mediators were examined. The results indicated that ASA VI improved left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), ±dP/dt, heart weight/body weight, right ventricular weight/body weight and lung weight/body weight (P<0.01, P<0.05). These were accompanied by the attenuation of cardiac fibrosis, IS and hydroxyproline concentration (P<0.01, P<0.05). ASA VI could decrease the levels of tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6), but increase IL-10 content (P<0.01, P<0.05). Furthermore, it also could raise the activities of catalase, superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), but reduce malonyldialdehyde (MDA) level (P<0.01, P<0.05). The results indicated that ASA VI improved cardiac function and myocardial fibrosis from myocardial ischemia injury, and this cardioprotection might be attributed to reduce oxidative stress and regulate inflammation mediators.

Fucoidan, a sulfated polysaccharide from brown algae, improves cognitive impairment induced by infusion of Aß peptide in rats.

Fucoidan is a complex sulfated polysaccharide, derived from marine brown seaweed. In the present study, we investigated the effects of fucoidan on improving learning and memory impairment in rats induced by infusion of Aß (1-40), and its possible mechanisms. The results indicated that fucoidan could ameliorate Aß-induced learning and memory impairment in animal behavioral tests. Furthermore, fucoidan reversed the decreased activity of choline acetyl transferase (ChAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and content of acetylcholine (Ach), as well as the increased activity of acetylcholine esterase (AchE) and content of malondialdehyde (MDA) in hippocampal tissue of Aß-injected rats. Moreover, these were accompanied by an increase of Bcl-2/Bax ratio and a decrease of caspase-3 activity. These results suggested that fucoidan could ameliorate the learning and memory abilities in Aß-induced AD rats, and the mechanisms appeared to be due to regulating the cholinergic system, reducing oxidative stress and inhibiting the cell apoptosis.

Neuroprotective effect of fucoidan on H2O2-induced apoptosis in PC12 cells via activation of PI3K/Akt pathway.

One of the plausible ways to prevent the reactive oxygen species (ROS)-mediated cellular injury is dietary or pharmaceutical augmentation of endogenous antioxidant defense capacity. In this study, we investigated the neuroprotective effect of fucoidan on H(2)O(2)-induced apoptosis in PC12 cells and the possible signaling pathways involved. The results showed that fucoidan inhibited the decrease of cell viability, scavenged ROS formation and reduced lactate dehydrogenase release in H(2)O(2)-induced PC12 cells. These changes were associated with an increase in superoxide dismutase and glutathione peroxidase activity, and reduction in malondialdehyde. In addition, fucoidan treatment inhibited apoptosis in H(2)O(2)-induced PC12 cells by increasing the Bcl-2/Bax ratio and decreasing active caspase-3 expression, as well as enhancing Akt phosphorylation (p-Akt). However, the protection of fucoidan on cell survival, p-Akt, the Bcl-2/Bax ratio and caspase-3 activity were abolished by pretreating with phosphatidylinositol-3-kinase (PI3K) inhibitor LY294002. In consequence, fucoidan might protect the neurocytes against H(2)O(2)-induced apoptosis via reducing ROS levels and activating PI3K/Akt signaling pathway.

Anti-inflammatory effects of sophocarpine in LPS-induced RAW 264.7 cells via NF-κB and MAPKs signaling pathways.

Sophocarpine, a tetracyclic quinolizidine alkaloid, is one of the most abundant active ingredients in Sophora alopecuroides L. Our previous studies have showed that sophocarpine exerts anti-inflammatory activity in animal models. In the present study, anti-inflammatory mechanisms of sophocarpine were investigated in lipopolysaccharide (LPS)-induced responses in RAW 264.7 cells. Furthermore, the cytotoxicity of sophocarpine was tested. The results indicated that sophocarpine could increase the LDH level and inhibit cell viability up to 800µg/ml, and which was far higher than that of the plasma concentration of sophocarpine in clinical effective dosage. The results also demonstrated that sophocarpine (50 and 100µg/ml) suppressed LPS-stimulated NO production and pro-inflammatory cytokines secretion, including tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6). These were associated with the decrease of the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Furthermore, sophocarpine inhibited LPS-mediated nuclear factor-κB (NF-κB) activation via the prevention of inhibitor κB (IκB) phosphorylation. Sophocarpine had no effect on the LPS-induced phosphorylation of extracellular signal-regulated kinase 1/2 (Erk1/2), whereas it attenuated the phosphorylation of p38 mitogen-activated protein (MAP) kinase and c-Jun NH(2)-terminal kinase (JNK). Our data suggested that sophocarpine exerted anti-inflammatory activity in vitro, and it might attribute to the inhibition of iNOS and COX-2 expressions via down-regulation of the JNK and p38 MAP kinase signal pathways and inhibition of NF-κB activation.

Fucoidan, a sulfated polysaccharide from brown algae, against myocardial ischemia-reperfusion injury in rats via regulating the inflammation response.

The aim of the study was to determine the effects of fucoidan on rat myocardial ischemia-reperfusion (I/R) model and elucidate the potential mechanisms. Myocardial I/R injury was induced by the occlusion of left anterior descending coronary artery for 30 min followed by reperfusion for 2h. After 2h reperfusion, hemodynamics parameters were detected. Blood samples were collected to determine serum levels of tumor necrosis factor-α (TNF-α) and interleukin 6, 10 (IL-6, 10). Hearts were harvested to assess histopathological changes, infarct size (IS), and the content of myeloperoxidase (MPO). The expression of high-mobility group box 1 (HMGB1), phosphor-IκB-α and phosphor-nuclear factor kappa B (NF-κB) were assayed by western blot. Compared with control group, treatment with fucoidan improved left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP) and the contractility index (P<0.05, P<0.01). Fucoidan reduced the myocardial IS, the levels of TNF-α and IL-6, and the activity of MPO (P<0.05, P<0.01). Fucoidan down-regulated the expression of HMGB1, phosphor-IκB-α and NF-κB, but increased the content of IL-10 when compared with control (P<0.05, P<0.01). Besides, the infiltration of polymorph nuclear leukocytes (PMNs) and histopathological damages in myocardium were decreased in fucoidan treated groups (PMNs, P<0.05, P<0.01). These findings revealed that the administration of fucoidan could regulate the inflammation response via HMGB1 and NF-κB inactivation in I/R-induced myocardial damage.

Sophocarpine administration preserves myocardial function from ischemia-reperfusion in rats via NF-κB inactivation.

ETHNOPHARMACOLOGICAL RELEVANCE: Sophora alopecuroides L. (the clinical usefulness of compound Kudouzi injection) has been used mainly for the treatment of fever, inflammation, edema and pain. Sophocarpine, a tetracyclic quinolizidine alkaloid, is one of the most abundant active ingredients in Sophora alopecuroides L. Sophocarpine injection (called the Kangke injection) has been demonstrated to have significant antivirus effects against coxsackievirus B3 and therapeutic effects for viral myocarditis in clinical. AIM OF THE STUDY: The present study was to evaluate the protective effect of sophocarpine on the inhibition of NF-kappaB (NF-κB) and effect on inflammatory markers during myocardial ischemia-reperfusion (I/R) injury in rat. MATERIALS AND METHODS: Myocardial I/R injury was induced by the occlusion of left anterior descending coronary artery for 30 min followed by reperfusion for 2 h. 2 h after reperfusion was established, the hemodynamics and infarct size were examined. Blood samples were collected for biochemical analysis. Expression of NF-κB and mitogen-activated protein kinases (MAPKs) in ischemic myocardial tissue were assayed by western blot. RESULTS: Administration of sophocarpine significantly improved cardiac function and reduced infarct size in I/R rat heart in vivo. Furthermore, sophocarpine ameliorated the contents of inflammatory mediators (tumor necrosis factor-alpha, TNF-α; interleukin-6, IL-6; IL-10), neutrophil infiltration and myeloperoxidase (MPO) activity. Interestingly, sophocarpine also significantly inhibited translocation of NF-κB, which was associated with attenuated phosphorylations of p38 and c-Jun NH2-terminal protein kinase (JNK). CONCLUSIONS: Inflammatory mediators, infiltration of neutrophil, and MPO were ameliorated via down-regulation of JNK and p38, and inactivation of NF-κB. This might be one of the important mechanisms of sophocarpine that protected myocardial injury from I/R.