Enantiomers or diastereomers of chiral bioactive compounds often exhibit different biological and toxicological properties. Here, we report the efficient synthesis of four stereoisomers of sphingosine and derivatization of unique chiral ceramides through a combinatorial chemistry by solid-phase activated resin ester. In addition, to test the effectivity of stereochemistry of ceramide, we demonstrated a cell-based assay of sphingomyelin synthase inhibition in the presence ofchiral unique ceramides, which suggested that libraries of this sort will be a rich source of biologically active synthetic molecules. 相似文献
The acute liver disease is involved in aberrant release of high-mobility group box 1 (HMGB1). Glycyrrhizin (GL), a traditional Chinese medicine for liver disease, binds to HMGB1, thereby inhibits tissue injury. However the mode of action of GL for chronic liver disease remains unclear.We investigated the effects of glycyrrhizin (GL) and its derivatives on liver differentiation using human iPS cells by using a flow cytometric analysis.GL promoted hepatic differentiation at the hepatoblast formation stage. The GL derivatives, 3-O-mono-glucuronyl 18β-glycyrrhetinic acid (Mono) and 3-O-[glucosyl (1 → 2)-glucuronyl] 18β-glycyrrhetinic acid increased AFP+ cell counts and albumin+ cell counts. Glucuronate conjugation seemed to be a requirement for hepatic differentiation. Mono exhibited the most significant hepatic differentiation effect.We evaluated the effects of (±)-2-(2,4-dichlorophenoxy) propionic acid (DP), a T1R3 antagonist, and sucralose, a T1R3 agonist, on hepatic differentiation, and found that DP suppressed Mono-induced hepatic differentiation, while sucralose promoted hepatic differentiation. Thus, GL promoted hepatic differentiation via T1R3 signaling. In addition, Mono increased β-catenin+ cell count and decreased Hes5+ cell count suggesting the involvement of Wnt and Notch signaling in GL-induced hepatic differentiation.In conclusion, GL exerted a hepatic differentiation effect via sweet receptor (T1R3), canonical Wnt, and Notch signaling. 相似文献
Organisms have a variety of three-dimensional (3D) structures that change over time. These changes include twisting, which is 3D deformation that cannot happen in two dimensions. Twisting is linked to important adaptive functions of organs, such as adjusting the orientation of leaves and flowers in plants to align with environmental stimuli (e.g. light, gravity). Despite its importance, the underlying mechanism for twisting remains to be determined, partly because there is no rigorous method for quantifying the twisting of plant organs. Conventional studies have relied on approximate measurements of the twisting angle in 2D, with arbitrary choices of observation angle. Here, we present the first rigorous quantification of the 3D twisting angles of Arabidopsis petioles based on light sheet microscopy. Mathematical separation of bending and twisting with strict definition of petiole cross-sections were implemented; differences in the spatial distribution of bending and twisting were detected via the quantification of angles along the petiole. Based on the measured values, we discuss that minute degrees of differential growth can result in pronounced twisting in petioles.
Based on morphological evidence, Bryozoa together with Phoronida and Brachiopoda are traditionally combined in the group Lophophorata, although this view has been recently challenged by molecular studies. The core of the concept lies in the presence of the lophophore as well as the nature and arrangement of the body cavities. Bryozoa are the least known in this respect. Here, we focused on the fine structure of the body cavity in 12 bryozoan species: 6 gymnolaemates, 3 stenolaemates and 3 phylactolaemates. In gymnolaemates, the complete epithelial lining of the body cavity is restricted to the lophophore, gut walls, and tentacle sheath. By contrast, the cystid walls are composed only of the ectocyst-producing epidermis without a coelothelium, or an underlying extracellular matrix; only the storage cells and cells of the funicular system contact the epidermis. The nature of the main body cavity in gymnolaemates is unique and may be considered as a secondarily modified coelom. In cyclostomes, both the lophophoral and endosaccal cavities are completely lined with coelothelium, while the exosaccal cavity only has the epidermis along the cystid wall. In gymnolaemates, the lophophore and trunk cavities are divided by an incomplete septum and communicate through two pores. In cyclostomes, the septum has a similar location, but no openings. In Phylactolaemata, the body cavity is undivided: the lophophore and trunk coeloms merge at the bases of the lophophore arms, the epistome cavity joins the trunk, and the forked canal opens into the arm coelom. The coelomic lining of the body is complete except for the epistome, lophophoral arms, and the basal portions of the tentacles, where the cells do not interlock perfectly (this design probably facilitates the ammonia excretion). The observed partitioning of the body cavity in bryozoans differs from that in phoronids and brachiopods, and contradicts the Lophophorata concept. 相似文献
Sea spiders are unique and poorly known marine chelicerates. Their larvae are even less studied, especially at the ultrastructural level. Here, we examined the hatchlings of Pycnogonum litorale (Strøm, 1,762) using histology, SEM and TEM. Existing classifications place these larvae among “typical” protonymphons, together with Nymphon brevirostre. Our results, however, revealed major differences between the two species. Hatchlings of P. litorale are endotrophic for 1–2 weeks, with yolk deposits in the body wall and a reduced secretory apparatus. They lack a body cavity, demonstrate an unusual modification of the midgut sheath cells and a complex subesophageal ganglion, which includes neuromeres of the prospective walking legs 1. These larvae also possess well-developed glia and complex sensory structures: eyes, V-shaped mechanoreceptive bristles, integrated chemo- and mechanoreceptors, and three types of concealed mechanoreceptors embedded into the body wall and only seen on the sections. In this paper we also propose a new interpretation of the pycnogonid larval types: we present a set of traits useful for diagnosis and a preliminary classification. Finally, we discuss the complexity of glial types in sea spiders and other arthropods. 相似文献
Photodynamic therapy (PDT) is a cancer therapy that uses a photosensitizer (PS) in the presence of oxygen molecules. Since singlet oxygen is highly reactive, it is important to deliver it to the target site. Thus, an efficient drug delivery system (DDS) is essential for enhancing the efficacy of such a treatment and protecting against the side effects of PDT. Here, we report on attempts to increase the therapeutic effect of PDT by using a DDS, a lipid nanoparticle (LNP). We prepared a porphyrin analog, rTPA (PS) that was encapsulated in LNPs using a microfluidic device. The findings indicated that the internal structure of the prepared particles changed depending on the amount of rTPA in LNPs. The photoactivity and cell-killing effect of PS in LNPs also changed when the amount of the cargo increased. These results suggest that the internal structure of LNPs is important factors that affect drug efficacy. 相似文献