A 3D-Bioprinted Multiple Myeloma Model.

Multiple myeloma (MM) is a malignancy of plasma cells accounting for ≈12% of hematological malignancies. In this study, the fabrication of a high-content in vitro MM model using a coaxial extrusion bioprinting method is reported, allowing formation of a human bone marrow-like microenvironment featuring an outer mineral-containing sheath and the inner soft hydrogel-based core. MM cells are mono-cultured or co-cultured with HS5 stromal cells that can release interleukin-6 (IL-6), where the cells show superior behaviors and responses to bortezomib in 3D models than in the planar cultures. Tocilizumab, a recombinant humanized anti-IL-6 receptor (IL-6R), is investigated for its efficacy to enhance the chemosensitivity of bortezomib on MM cells cultured in the 3D model by inhibiting IL-6R. More excitingly, in a proof-of-concept demonstration, it is revealed that patient-derived MM cells can be maintained in 3D-bioprinted microenvironment with decent viability for up to 7 days evaluated, whereas they completely die off in planar culture as soon as 5 days. In conclusion, a 3D-bioprinted MM model is fabricated to emulate some characteristics of the human bone marrow to promote growth and proliferation of the encapsulated MM cells, providing new insights for MM modeling, drug development, and personalized therapy in the future.

Physicochemical characterization, potential antioxidant and hypoglycemic activity of polysaccharide from Sargassum pallidum.

A polysaccharide, designated as PSP-1, was isolated and purified from Sargassum pallidum. Physicochemical characterization showed that PSP-1 with the average molecular weight of 1.036 × 106 Da was composed of fucose, arabinose, galactose, glucose, xylose, mannose, galacturonic acid and glucuronic acid in a molar ratio of 18.45:2.15:19.06:1.89:16.07:1.00:5.74:20.09. The results of antioxidant assays indicated that PSP-1 had good DPPH radical scavenging activity, hydroxyl radical scavenging activity, cellular antioxidant activity, and reactive oxygen species inhibition activity, and could significantly improve cellular antioxidant enzymes of ABAP-induced HepG2 cell model. The results of hypoglycemic assays showed that PSP-1 possessed favorable α-amylase and α-glucosidase inhibitory activities, and could remarkably enhance glucose consumption, glycogen synthesis and the activities of pyruvate kinase and hexokinase in insulin-resistance HepG2 cells. The results suggest that PSP-1 can be exploited as a potential antioxidant and hypoglycemic candidate for functional and nutraceutical applications.

Structure and in vitro hypoglycemic activity of a homogenous polysaccharide purified from Sargassum pallidum.

This study aimed at investigating the structure, hypoglycemic activity and the underlying mechanism of a homogeneous polysaccharide (PSP-2) purified from Sargassum pallidum. Structural characterization revealed that PSP-2 with a molecular weight of 144.8 kDa was composed of fucose (21.6%), arabinose (2.5%), galactose (22.4%), glucose (2.2%), xylose (18.8%), mannose (1.2%), glucuronic acid (7.7%) and galacturonic acid (23.6%). The backbone chain of PSP-2 was composed of →1)-ß-d-Xylp-(3→, →1,3)-ß-l-Fucp-(4→, →1)-α-d-Galp-(6→, and →1)-α-d-GlcpNAc-(2→, and the side chains were composed of →1,3,6)-α-d-Galp-(2→, →3)-ß-l-Fucp-(1,4→, ß-d-GalpNAc-(1→, and α-d-Manp-(1→. In vitro hypoglycemic assays indicated that PSP-2 could significantly enhance glucose consumption, glycogen synthesis, and pyruvate kinase (PK) and hexokinase (HK) activities of insulin-resistant HepG2 cells. Furthermore, the underlying mechanistic studies revealed that PSP-2 could ameliorate insulin resistance by up-regulating the expression levels of insulin receptor substrate-1 (IRS-1), glycogen synthase (GS), phosphoinositide-3-kinase (PI3K) and glucose transporter-4 (GLUT4). These results suggested that PSP-2 may be a potential candidate for the prevention and treatment of Type 2 diabetes mellitus.

Preliminary characterization, antioxidant and α-glucosidase inhibitory activities of polysaccharides from Mallotus furetianus.

A purified polysaccharide, designated as MFP-2A, was isolated from Mallotus furetianus (Bail) Muell Arg. The primary structure characteristics were determined by HPGPC, HPLC, FT-IR, methylation analysis, NMR, SEM and AFM. The results showed that MFP-2A was a homogeneous heteropolysaccharide with an average molecular weight of 25.96 KDa. The monosaccharide composition was consisted of mannose, galactose, arabinose, galacturonic acid and glucose with a molar ratio of 3.05:2.84:1.84:0.86:1.41. In addition, methylation and NMR analysis revealed that the main glycosidic bonds of MFP-2A were comprised of 1,4,6-linked-ß-d-Galp, 1,3,6-linked-ß-d-Manp, 1,5-linked-α-l-Araf, 1-linked-α-l-Araf, 1,4-linked-α-d-GalAp and 1,4-linked-α-d-Glcp residues. Moreover, MFP-2A also exhibited significant free radical scavenging ability and α-glucosidase inhibitory activities in vitro. Overall, these results demonstrated that MFP-2A from Mallotus furetianus (Bail) Muell Arg could serve as a potential anti-diabetic and functional food.

Sulfated modification, characterization, antioxidant and hypoglycemic activities of polysaccharides from Sargassum pallidum.

The aim of this study was to investigate the effect of sulfated modification on the in vitro antioxidant and hypoglycemic activities of Sargassum pallidum polysaccharides (SPP). Three sulfated derivatives (S-SPP1-4, S-SPP1-6 and S-SPP1-8) were prepared using chlorosulfonic acid-pyridine method under different reaction conditions. Physicochemical characterization indicated that sulfated modification had successfully occurred. The degrees of substitution (DS) of S-SPP1-4, S-SPP1-6 and S-SPP1-8 were determined to be ranging from 0.85 to 1.19. Sulfated modification resulted in some changes in chemical component, molecular weight and monosaccharide composition of SPP. Among these sulfated polysaccharides, S-SPP1-4 exhibited the best DPPH and ABTS radical scavenging activities, while S-SPP1-8 exhibited the best α-glucosidase inhibitory activity and promoting-effect on glucose consumption in insulin resistant (IR)-HepG2 cells. Furthermore, all the sulfated derivatives exhibited better hypoglycemic ability than native SPP. These results suggest that appropriately sulfated modification could enhance the antioxidant and hypoglycemic activities of S. pallidum polysaccharides, which might be used as an alternative derivative of natural antioxidant and hypoglycemic agent.

Structural characterization and in vitro fermentation of a novel polysaccharide from Sargassum thunbergii and its impact on gut microbiota.

The aim of the present study was to investigate structural characteristic and in vitro fermentation of a novel polysaccharide named ST-P2 from Sargassum thunbergii by human fecal inoculums, and its impact on human colonic microbiota. The results showed that ST-P2 was homogeneous with molecular weight of 48,788 Da, and consisted of arabinose, galactose, glucose, xylose, and mannose. The main linkage types were identified as (1 → 5)-α-L-Araf, (1 → 3)-α-L-Manp, (1 → 3,6)-ß-D-Galp, (1 → 6)-α-D-Glcp, and (1 → 3)-ß-D-Xylp, respectively. After 48 h fermentation, 67.83 ±â€¯1.15% of total carbohydrate was utilized by colonic microbiota. The pH value in the fecal culture significantly decreased from 6.09 ±â€¯0.11 to 4.70 ±â€¯0.04. The concentrations of total short chain fatty acids, acetic, propionic, n-butyric and n-valeric acids significantly increased compared to the blank. ST-P2 could remarkably modulate the composition and abundance of beneficial microbiota. These results suggest that ST-P2 could potentially be a functional food aimed at promoting the gut health.

Physicochemical characterization and in vitro hypoglycemic activities of polysaccharides from Sargassum pallidum by microwave-assisted aqueous two-phase extraction.

Microwave-assisted aqueous two-phase extraction (MAATPE) was applied for simultaneous extraction and separation of polysaccharides from Sargassum pallidum (SPPs). The optimal extraction parameters, physicochemical properties, and hypoglycemic activities in vitro of SPPs were investigated. The results revealed that the optimal extraction conditions were as follows: 21.0% ethanol (w/w) and 22.0% ammonium sulfate (w/w) for ATPS, ratio of material to liquid 1:60 (g/mL), extraction time 15 min, microwave power 830 W, and extraction temperature 95 °C. Under the optimal these conditions, the maximum yields of SPPs were 0.75 ±â€¯0.04% of the top phase (SPP-1) and 6.81 ±â€¯0.33% of the bottom phase (SPP-2). SPP-1 and SPP-2 were homogeneous with molecular weights of 1518.6 and 50.6 kDa, respectively. SPP-1 mainly consisted of fucose, galactose, mannose, and glucuronic acid with a molar ratio of 4.97:9.75:6.44:6.07, whereas SPP-2 was mainly composed of fucose, galactose, glucose, and mannose with a molar ratio of 4.20:2.88:18.05:7.83. SPP-1 and SPP-2 exhibited favorable α-amylase and α-glucosidase inhibitory activities, and could remarkably improve glucose consumption in insulin resistance (IR) model cells. Notably, SPP-1 exhibited stronger α-glucosidase inhibitory activity than SPP-2, and even was comparable with acarbose.