Mutations of the endothelial BMP9/10 receptors Alk1 and endoglin are associated with vascular malformations in hereditary hemorrhagic telangiectasia (HHT). Baeyens et al. report that fluid flow potentiates BMP activation of Alk1 signaling to stabilize blood vessels. HHT lesions thus result from a defect in a synergistic mechanical/biochemical signaling pathway.

Human and animal studies suggest that acupuncture produces many beneficial effects through the central nervous system. However, the neural substrates of acupuncture actions are not completely clear to date. fMRI studies at Hegu (LI4) and Zusanli (ST36) indicated that the limbic system may play an important role for acupuncture effects. To test if this finding applies to other major classical acupoints, fMRI was performed on 10 healthy adults during manual acupuncture at Taichong (LV3), Xingjian (LV2), Neiting (ST44), and a sham point on the dorsum of the left foot. Although certain differences could be observed between real and sham points, the hemodynamic response (BOLD signal changes) and psychophysical response (sensory experience) to acupuncture were generally similar for all four points. Acupuncture produced extensive deactivation of the limbic-paralimbic-neocortical system. Clusters of deactivated regions were seen in the medial prefrontal cortex (frontal pole, pregenual cingulate), the temporal lobe (amygdala, hippocampus, and parahippocampus) and the posterior medial cortex (precuneus, posterior cingulate). The sensorimotor cortices (somatosensory cortices, supplementary motor cortex), thalamus and occasional paralimbic structures such as the insula and anterior middle cingulate cortex showed activation. Our results provide additional evidence in support of previous reports that acupuncture modulates the limbic-paralimbic-neocortical network. We hypothesize that acupuncture may mediate its antipain, antianxiety, and other therapeutic effects via this intrinsic neural circuit that plays a central role in the affective and cognitive dimensions of pain as well as in the regulation and integration of emotion, memory processing, autonomic, endocrine, immunological, and sensorimotor functions.

Fucoidan is a polysaccharide largely made up of l-fucose and sulfate groups. Fucoidan is favorable worldwide, especially amongst the food and pharmaceutical industry as a consequence of its promising therapeutic effects. Its applaudable biological functions are ascribed to its unique biological structure. Classical bioactivities associated with fucoidan include anti-oxidant, anti-tumor, anti-coagulant, anti-thrombotic, immunoregulatory, anti-viral and anti-inflammatory effects. More recently, a variety of in vitro and in vivo studies have been carried out to further highlight its therapeutic potentials. This review focuses on the progress towards understanding fucoidan and its biological activities, which may be beneficial as a future therapy. Hence, we have summarized in vitro and in vivo studies that were done within the current decade. We expect this review and a variety of others can contribute as a theoretical basis for understanding and inspire further product development of fucoidan.

Integrins mediate cell adhesion to extracellular matrix and transduce signals bidirectionally across the membrane. Integrin αVβ3 has been shown to play an essential role in tumor metastasis, angiogenesis, hemostasis and phagocytosis. Integrins can take several conformations, including the bent and extended conformations of the ectodomain, which regulate integrin functions. Using a biomembrane force probe, we characterized the bending and unbending conformational changes of a single integrin αVβ3 molecule on a living cell surface in real-time. We measured the probabilities of conformational changes, rates and speeds of conformational transitions, and the dynamic equilibrium between the two conformations, which were regulated by tensile force, dependent on the ligand, and altered by point mutations. These findings provide insights into how αVβ3 acts as a molecular machine and how its physiological function and molecular structure are coupled at the single molecule level.

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Sargassum f usiforme fucoidan (SFF) exhibits diverse biological activities. Insulin resistance (IR) implicated in type 2 diabetes (T2D) has become an epidemic health issue worldwide. In this study, we investigated whether SFF can improve insulin sensitivity in high-fat diet (HFD)-fed mice. Our present data showed that SFF significantly reduced fasting blood glucose and IR index along with improved glucose tolerance. Impaired phosphorylation of Akt was also restored by SFF. Furthermore, SFF decreased the levels of MDA and 4-HNE-modified protein and increased GSH/GSSG ratio as well as elevated antioxidant enzymes and activated Nrf2 signaling. SFF also increased the abundance and diversity of gut microbiota in the obese mice, as well as improved intestinal integrity and inflammation. Our findings suggested that SFF ameliorated HFD-induced IR through activating the Nrf2 pathway, remodeling gut microbiota, and reducing intestinal inflammation, thus providing a novel perspective into the treatment strategy on metabolic disease.

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