Injectable poly-D,L-lactic acid (PDLLA) is a relatively new subdermal biostimulatory filler that is used for the treatment of deep and shallow facial wrinkles. PDLLA is supplied as lumps of lyophilized powder in vials. It requires reconstitution with sterile water for injection (SWFI) into a homogeneous suspension before administration. The reconstitution methods recommended by the manufacturer are hand-shaking and vortex generator-assisted agitation. However, these methods have some disadvantages. Handshaking agitation, which is used for reconstitution prior to correction of shallow wrinkles (a process that requires 8 mL of SWFI), is an exhausting process. Vortex generatorassisted agitation, which is used for reconstitution before the correction of deep wrinkles (requiring 1.4 mL of SWFI), is time-consuming. To address these drawbacks, we propose a simple, quick, effortless, and efficient “back-and-forth” method for the reconstitution of injectable PDLLA. Using this technique, PDLLA can be easily prepared using large or small volumes of SWFI for different purposes related to facial volumization.

Resveratrol, an anti-inflammatory agent, can inhibit pro-inflammatory mediators by activating Sirt1, which is a class III histone deacetylase. However, whether resveratrol can regulate inhibitory or anti-inflammatory molecules has been less studied. FcγRIIB, a receptor for IgG, is an essential inhibitory receptor of B cells for blocking B-cell receptor-mediated activation and for directly inducing apoptosis of B cells. Because mice deficient in either Sirt1 or FcγRIIB develop lupus-like diseases, we investigated whether resveratrol can alleviate lupus through FcγRIIB. We found that resveratrol enhanced the expression of FcγRIIB in B cells, resulting in a marked depletion of plasma cells in the spleen and notably in the bone marrow, thereby decreasing serum autoantibody titers in MRL/lpr mice. The upregulation of FcγRIIB by resveratrol involved an increase of Sirt1 protein and deacetylation of p65 NF-κB (K310). Moreover, increased binding of phosphor-p65 NF-κB (S536) but decreased association of acetylated p65 NF-κB (K310) and phosphor-p65 NF-κB (S468) to the −480 promoter region of Fcgr2b gene was responsible for the resveratrol-mediated enhancement of FcγRIIB gene transcription. Consequently, B cells, especially plasma cells, were considerably reduced in MRL/lpr mice, leading to improvement of nephritis and prolonged survival. Taken together, we provide evidence that pharmacological upregulation of FcγRIIB expression in B cells via resveratrol can selectively reduce B cells, decrease serum autoantibodies and ameliorate lupus nephritis. Our findings lead us to propose FcγRIIB as a new target for therapeutic exploitation, particularly for lupus patients whose FcγRIIB expression levels in B cells are downregulated.
Animals ; Apoptosis ; Autoantibodies ; B-Lymphocytes* ; Bone Marrow ; Histone Deacetylases ; Humans ; Immunoglobulin G ; Lupus Nephritis ; Mice ; Nephritis ; Plasma Cells ; Promoter Regions, Genetic ; Spleen ; Up-Regulation*

C-Glycosides are important natural products with various bioactivities. In plant biosynthetic pathways, the C-glycosylation step is usually catalyzed by C-glycosyltransferases (CGTs), and most of them prefer to accept uridine 5'-diphosphate glucose (UDP-Glc) as sugar donor. No CGTs favoring UDP-rhamnose (UDP-Rha) as sugar donor has been reported, thus far. Herein, we report the first selective C-rhamnosyltransferase VtCGTc from the medicinal plant Viola tricolor. VtCGTc could efficiently catalyze C-rhamnosylation of 2-hydroxynaringenin 3-C-glucoside, and exhibited high selectivity towards UDP-Rha. Mechanisms for the sugar donor selectivity of VtCGTc were investigated by molecular dynamics (MD) simulations and molecular mechanics with generalized Born and surface area solvation (MM/GBSA) binding free energy calculations. Val144 played a vital role in recognizing UDP-Rha, and the V144T mutant could efficiently utilize UDP-Glc. This work provides a new and efficient approach to prepare flavonoid C-rhamnosides such as violanthin and iso-violanthin.