Cu-Tremella fuciformis polysaccharide-based tumor microenvironment-responsive injectable gels for cuproptosis-based synergistic osteosarcoma therapy.

Cuproptosis affects osteosarcoma locally, and the exploitation of cuproptosis-related biomaterials for osteosarcoma treatment is still in its infancy. We designed and synthesized a novel injectable gel of Cu ion-coordinated Tremella fuciformis polysaccharide (TFP-Cu) for antiosteosarcoma therapy. This material has antitumor effects, the ability to stimulate immunity and promote bone formation, and a controlled Cu2+ release profile in smart response to tumor microenvironment stimulation. TFP-Cu can selectively inhibit the proliferation of K7M2 tumor cells by arresting the cell cycle and promoting cell apoptosis and cuproptosis. TFP-Cu also promoted the M1 polarization of RAW264.7 cells and regulated the immune microenvironment. These effects increased osteogenic gene and protein expression in MC3T3-E1 cells. TFP-Cu could significantly limit tumor growth in tumor-bearing mice by inducing tumor cell apoptosis and improving the activation of anti-CD8 T cell-mediated immune responses. Therefore, TFP-Cu could be a potential candidate for treating osteosarcoma and bioactive drug carrier for further cancer-related applications.

Orbital topological edge states and phase transitions in one-dimensional acoustic resonator chains.

Topological phases of matter have attracted significant attention in recent years, due to the unusual robustness of their response to defects and disorder. Various research efforts have been exploring classical and quantum topological wave phenomena in engineered materials, in which different degrees of freedom (DoFs) - for the most part based on broken crystal symmetries associated with pseudo-spins - induce synthetic gauge fields that support topological phases and unveil distinct forms of wave propagation. However, spin is not the only viable option to induce topological effects. Intrinsic orbital DoFs in spinless systems may offer a powerful alternative platform, mostly unexplored to date. Here we reveal orbital-selective wave-matter interactions in acoustic systems supporting multiple orbital DoFs, and report the experimental demonstration of disorder-immune orbital-induced topological edge states in a zigzag acoustic 1D spinless lattice. This work expands the study of topological phases based on orbitals, paving the way to explore other orbital-dependent phenomena in spinless systems.

Decorated bacteria-cellulose ultrasonic metasurface.

Cellulose, as a component of green plants, becomes attractive for fabricating biocompatible flexible functional devices but is plagued by hydrophilic properties, which make it easily break down in water by poor mechanical stability. Here we report a class of SiO2-nanoparticle-decorated bacteria-cellulose meta-skin with superior stability in water, excellent machining property, ultrathin thickness, and active bacteria-repairing capacity. We further develop functional ultrasonic metasurfaces based on meta-skin paper-cutting that can generate intricate patterns of ~10 µm precision. Benefited from the perfect ultrasound insulation of surface Cassie-Baxter states, we utilize meta-skin paper-cutting to design and fabricate ultrathin (~20 µm) and super-light (<20 mg) chip-scale devices, such as nonlocal holographic meta-lens and the 3D imaging meta-lens, realizing complicated acoustic holograms and high-resolution 3D ultrasound imaging in far fields. The decorated bacteria-cellulose ultrasonic metasurface opens the way for exploiting flexible and biologically degradable metamaterial devices with functionality customization and key applications in advanced biomedical engineering technologies.

Calcitriol-Loaded Multifunctional Nanospheres with Superlubricity for Advanced Osteoarthritis Treatment.

Osteoarthritis (OA) is characterized by the lubrication dysfunction of a cartilage sliding interface caused by chronic joint inflammation, and effective nonsurgical therapy for advanced OA remains lacking. Addressing chronic joint inflammation, lubrication dysfunction, and cartilage-tissue degradation simultaneously may hopefully tackle this challenge. Herein, we developed superlubricative zein@alginate/strontium@calcitriol (ZASC) nanospheres to treat advanced OA. ZASC was confirmed to significantly improve joint lubrication through traditional tribological tests and our proposed tribological experiment to mimic the intra-articular condition based on the human medial tibiofemoral joint tissues. This finding was attributed to the hydration lubrication formed around the alginate-strontium spheres that enabled ball-bearing lubrication and the filling of cartilage defects. Moreover, ZASCs that released calcitriol in a sustained manner showed proliferative, anti-inflammatory, and anti-apoptosis effects in vitro. Further experiments demonstrated that ZASC exerted chondroprotective effects by inhibiting the breakdown of the extracellular matrix in patient-derived OA cartilage explants. In vivo results demonstrated that ZASC can effectively maintain a normal gait to improve joint function, inhibit abnormal bone remodeling and cartilage degradation in early OA and can effectively reverse the advanced OA progression. Therefore, ZASC is a potentially nonsurgical therapeutic strategy for advanced OA treatments.

Surface modifications of titanium dental implants with strontium eucommia ulmoides to enhance osseointegration and suppress inflammation.

BACKGROUND: Titanium (Ti) is now widely used as implant material due to its excellent mechanical properties and superior biocompatibilities, while its inert bioactivities might lead to insufficient osseointegration, and limit its performance in dental applications. METHODS: We introduced a robust and simple approach of modifying titanium surfaces with polysaccharide complexes. Titanium samples were subjected to hydrothermal treatment to create a uniform porous structure on the surface, followed by coating with a bioinspired and self-assembly polydopamine layer. Strontium Eucommia Ulmoides Polysaccharide (EUP-Sr) complexes are then introduced to the polydopamine-coated porous titanium. Multiple morphological and physiochemical characterizations are employed for material evaluation, while cell proliferation and gene expression tests using macrophages, primary alveolar bone osteoblasts, and vascular endothelial cells are used to provide an overall insight into the functions of the product. The significances of statistical differences were analyzed using student's t-test. RESULTS: Microscopic and spectrometric characterizations confirmed that the Ti surface formed a porous structure with an adequate amount of EUP-Sr loading. The attachment was attributed to hydrogen bonding between the ubiquitous glycosidic linkage of the polysaccharide complex and the ring structure of polydopamine, yet the loaded EUP-Sr complex can be gradually released, consequently benefiting the neighboring microenvironment. Cell experiments showed no cytotoxicity of the material, and the product showed promising anti-inflammation, osseointegration, and angiogenesis properties, which were further confirmed by in vivo evaluations. CONCLUSION: We believe the EUP-Sr modified titanium implant is a promising candidate to be used in dental applications with notable osteoimmunomodulation and angiogenesis functions. And the novel technique proposed in this study would benefit the modification of metal/inorganic surfaces with polysaccharides for future research.

The development of novel multifunctional drug system 7,8-DHF@ZIF-8 and its potential application in bone defect healing.

Physical exercise has long been considered an essential regulator of bone formation. Recent studies have shown that brain-derived neurotrophic factor (BDNF) is an important cytokine released during physical exercise to promote osteogenic differentiation and facilitate the bone defect healing process. In this study, we developed a multifunctional system 7,8-DHF@ZIF-8, which combines the superior osteogenesis and angiogenesis properties of ZIF-8 and the unique capability of 7,8-DHF to mimic the function of BDNF to compensate for the routine physical exercise missed during the bone defect period. Various material characterizations were performed to confirm the successful synthesis of 7,8-DHF@ZIF-8. Drug release experiments suggested that 7,8-DHF@ZIF-8 could achieve slow diffusive release under physiological conditions within seven days. In vitro cell experiments indicated that low concentrations of ZIF-8 and 7,8-DHF@ZIF-8 could significantly promote the proliferation of MC3T3-E1 cells. Moreover, as proved by RT-QPCR analysis, incorporating 7,8-DHF into ZIF-8 could further enhance osteogenesis and angiogenesis-related gene expression. Therefore, we believe that the multifunctional drug system 7,8-DHF@ZIF-8 should have promising applications to facilitate bone defect healing.

Strontium-modified porous polyetheretherketone with the triple function of osteogenesis, angiogenesis, and anti-inflammatory for bone grafting.

Polyetheretherketone (PEEK) is a potential bone repair material because of its stable chemical and good mechanical properties. However, the biological inertness of PEEK limits its clinical application. Sr2+ has multi biological functions, including promoting bone formation and blood vessel regeneration and inhibiting inflammation. In this paper, PEEK was modified with Sr2+ with the purpose to construct PEEK bone graft material with triple functions of osteogenesis, angiogenesis, and anti-inflammatory. The results showed that Sr-modified PEEK could stably release Sr2+ for a long time in the PBS solution, and indeed could promote the proliferation and differentiation of osteoblasts, promote angiogenesis, and inhibit inflammation. Therefore, it is believed that this multifunctional PEEK with Sr2+ should show great promise for clinical applications in bone repair.

A cannabidiol-containing alginate based hydrogel as novel multifunctional wound dressing for promoting wound healing.

In addition to preventing infection and promoting angiogenesis, novel hydrogel dressings are highly expected to possess the potential to scavenge reactive oxygen species (ROS) and reduce inflammatory responses during the wound healing process. In this study, we designed and fabricated a hydrogel dressing (CBD/Alg@Zn) containing cannabidiol (CBD) based on the ion crosslinked interaction between Zn2+ ions and the alginate polymer (Alg). The as-fabricated hydrogel exhibited a suitable swelling ratio, sufficient thermal stability, and stable rheological property. In vitro biological activity experiments indicated that the hydrogel has good biocompatibility, antibacterial activity, and angiogenesis properties. Moreover, it could significantly scavenge DPPH (2,2-diphenyl-1-picrylhydrazyl) free radicals and reduce the inflammatory response. In vivo studies revealed that the CBD/Alg@Zn hydrogel significantly facilitated the wound healing process by controlling the inflammatory infiltration, promoting collagen deposition and the granulation tissue, and benefiting the formation of blood vessels. We, therefore, suggested that CBD/Alg@Zn hydrogel should be a potential candidate material for wound dressing and skin tissue engineering.

Surface Modification of Poly(ether ether ketone) by Simple Chemical Grafting of Strontium Chondroitin Sulfate to Improve its Anti-Inflammation, Angiogenesis, Osteogenic Properties.

Besides inducing osteogenic differentiation, the surface modification of poly(ether ether ketone) (PEEK) is highly expected to improve its angiogenic activity and reduce the inflammatory response in the surrounding tissue. Herein, strontium chondroitin sulfate is first attempted to be introduced into the surface of sulfonated PEEK (SPEEK-CS@Sr) based on the Schiff base reaction between PEEK and ethylenediamine (EDA) and the amidation reaction between EDA and chondroitin sulfate (CS). The surface characteristics of SPEEK-CS@Sr implant are systematically investigated, and its biological properties in vitro and in vivo are also evaluated. The results show that the surface of SPEEK-CS@Sr implant exhibits a 3D microporous structure and good hydrophilicity, and can steadily release Sr ions. Importantly, the SPEEK-CS@Sr not only displays excellent biocompatibility, but also can remarkably promote cell adhesion and spread, improve osteogenic activity and angiogenic activity, and reduce the inflammatory response compared to the original PEEK. Therefore, this study presents the surface modification of PEEK material by simple chemical grafting of strontium chondroitin sulfate to improve its angiogenesis, anti-inflammation, and osteogenic properties, and the as-fabricated SPEEK-CS@Sr has the potential to serve as a promising orthopedic implant in bone tissue engineering.

Chondroitin sulfate zinc with antibacterial properties and anti-inflammatory effects for skin wound healing.

A chondroitin sulfate zinc (CSZn) complex was prepared by an ion-exchange method. The purified product was characterized by energy-dispersive X-ray spectroscopy, high-performance chromatography, elemental analysis, Fourier transform infrared spectroscopy, inductively coupled mass spectrometry, and nuclear magnetic resonance spectroscopy. The CSZn demonstrated antibacterial activity against Escherichia coli and Staphylococcus aureus and satisfied MTT cell viability (NIH3T3 fibroblasts) at ≤50 µg/mL. RT-PCR demonstrated significant promotion by CSZn of fibroblast growth factor beta (ß-FGF), collagen III (COLIIIα1), vascular endothelial growth factor (VEGF) and reduction of cytokines IL-6, IL-1ß & TNF-alpha. An in vivo rat full-thickness wound healing model demonstrated significant wound healing of CSZn relative to controls of saline treatment, zinc chloride treatment and chondroitin treatment. CSZn has demonstrated promising antibacterial and wound healing properties making it deserving of consideration for more advanced wound healing applications.

Structure of a laminarin-type ß-(1→3)-glucan from brown algae Sargassum henslowianum and its potential on regulating gut microbiota.

A homogeneous polysaccharide named SHNP with apparent molecular weight of 8.4 kDa was purified from brown algae Sargassum henslowianum using ethanol precipitation, ion-exchange chromatography, and gel-filtration column chromatography. Structural analyses reveal that SHNP is completely composed of glucose, and its backbone consists of ß-D-(1→3)-Glcp with side chains comprising t-ß-D-Glcp attached at the O-6 position. Thus, SHNP is a laminarin-type polysaccharide. In vitro fermentation test results showed that SHNP was digested by gut microbiota; the pH value in the fecal culture of SHNP was significantly decreased; and total short-chain fatty acids, acetic, propionic and n-butyric acids were significantly increased. Furthermore, SHNP regulated the intestinal microbiota composition by stimulating the growth of species belonging to Enterobacteriaceae while depleting Haemophilus parainfluenzae and Gemmiger formicilis. Taken together, these results indicate that SHNP has the potential for regulating gut microbiota, but its specific role in the regulation requires to be further investigated.

A novel inulin-type fructan from Asparagus cochinchinensis and its beneficial impact on human intestinal microbiota.

A purified inulin-type fructan named ACNP (Asparagus cochinchinensis neutral polysaccharide) with apparent molecular weight of 2690 Da was obtained from Asparagus cochinchinensis (Lour.) Merr. by ion-exchange and gel-filtration column chromatography. Structural analyses reveal that ACNP has a linear backbone composed of 2,1-ß-D-Fruf residues, ending with a (1→2) bonded α-D-Glcp. The impacts of ACNP on gut microbiota were then investigated by in vitro fermentation with human fecal cultures. The results showed that ACNP was digested by gut microbiota, while the pH value in the fecal culture of ACNP was greatly decreased, and total short-chain fatty acids, acetic, propionic, i-valeric and n-valeric acids were significantly increased. Moreover, ACNP regulated the fecal microbiota composition by stimulating the growth of Prevotella, Megamonas, and Bifidobacterium while depleting Haemophilus. Collectively, these results indicated that ACNP beneficially regulates gut microbiota, which thus suggested that ACNP has the potential to be used as a dietary supplement or drug to improve health.

Structural characterization and antiviral activity of two fucoidans from the brown algae Sargassum henslowianum.

Purified fucoidans SHAP-1 and SHAP-2 with apparent molecular weights of 6.55 × 105 and 5.89 × 105, respectively, were isolated from Sargassum henslowianum by ion-exchange and gel-filtration column chromatography. They are both composed of fucose and galactose at a ratio of around 3:1 and 31.9% sulfate. The backbone of two fucoidans consists of α-(1→3)-linked L-Fucp residues which are mainly sulfated on the C-2 and C-4 positions. Side chains composed of terminally linked α-L-Fucp and α-D-Galp residues, and (1→2)-, (1→6)-, and (1→2,6)-linked ß-D-Galp residues attach mainly at O-4 position of backbone residues. Antiviral test showed that the IC50 values of SHAP-1 and SHAP-2 against HSV-1 were estimated to be 0.89 and 0.82 µg/mL by plaque reduction assay, respectively, whereas both as low as 0.48 µg/mL against HSV-2. The antiviral mechanism of the fucoidans might be at least through blocking HSV-2 virion adsorption to host cells. These results suggest that the fucoidans have potential clinical applications.

Structural characterization of three polysaccharides from the roots of Codonopsis pilosula and their immunomodulatory effects on RAW264.7 macrophages.

Three polysaccharides were isolated from the roots of Codonopsis pilosula by ion-exchange and gel-filtration chromatography. They were named RCNP, RCAP-1, and RCAP-2, and had apparent molecular weights of 1.14 × 104, 5.09 × 104, and 2.58 × 105, respectively. Their structures were characterized by HPGPC, chemical derivative analysis, GC-MS and NMR analyses. Results showed that RCNP contained arabinan and arabinogalactan regions. The arabinan region had a main chain comprising (1 → 5)-linked Araf residues, and the side chains branched at the O-3 position by the single Araf residues. The arabinogalactan region comprised alternating (1 → 4)-, (1 → 6)- or (1 → 3)-linked Galp along with small amounts of branches mainly at the O-3 position of the (1 → 6)-linked Galp or O-6 position of the (1 → 3)-linked Galp residues by terminally linked Araf residues. RCAP-1 and RCAP-2 were highly methyl-esterified pectin-type polysaccharides with long homogalacturonan regions interrupted by a short rhamnogalacturonan I (RG-I) region. The side chains of the RG-I region consisted of (1 → 2)-linked Rha residues attached to the position O-4 of rhamnose. Their degrees of methyl-esterification were approximately 60.6% and 68.1%, respectively. Bioactivity tests showed that RCAP-1 and RCAP-2 exerted a significant immunostimulatory effect based on NO production from RAW264.7 macrophages. These results suggested that these two pectin-type polysaccharides were potential immunostimulation agents.

Structural characterization of a polysaccharide from Coreopsis tinctoria Nutt. and its function to modify myeloid derived suppressor cells.

Coreopsis tinctoria Nutt. (C. tinctoria) is a natural plant with many health benefits, such as clearing heat and toxic materials. In this study, we investigate the effect of a polysaccharide from C. tinctoria, aiming at improving the tumor microenvironment, which is associated with non-resolving inflammation. Through combining ion-exchange and gel permeation chromatography, a polysaccharide named CTAP-3 is purified from the crude polysaccharides of C. tinctoria. The structure of CTAP-3 is characterized through high-performance gel permeation chromatography, chemical derivative analyses, GC-MS, FT-IR, and NMR. Results reveal that CTAP-3 consists of predominant amounts (87.2%) of galacturonic acid (GalA) residues, small amounts of arabinose (Ara) and rhamnose (Rham), and trace amounts of galactose (Gal). CTAP-3 is deduced to be native pectin-type polysaccharide containing a homo-galacturanan backbone consisting of α-(1 → 4)-linked GalAp and methyl-esterified α-(1 → 4)-linked GalAp residues in the ratio of 4:1. When myeloid-derived suppressor cells (MDSCs) are treated by CTAP-3, its suppressive effect on T cell proliferation is impaired. This result indicates that CTAP-3 is a candidate drug for improving the tumor microenvironment.

Structural characterization of a pectin-type polysaccharide from Curcuma kwangsiensis and its effects on reversing MDSC-mediated T cell suppression.

Myeloid-derived suppressor cells (MDSCs) accumulate in tumor-bearing hosts and play a major role in tumor-induced immunosuppression. The potent modulatory effects of polysaccharides on the innate and adaptive immune system stimulate antitumor responses. In this study, a polysaccharide with an apparent molecular weight of 14.0 kD was isolated from Curcuma kwangsiensis and designated as CKAP-2. The polysaccharide was characterized through high-performance gel permeation chromatography, chemical derivative analyses, GC-MS, FT-IR, and NMR. Results revealed that CKAP-2 is a highly methyl-esterified pectin-type polysaccharide. It is predominantly composed of a homogalacturonan region and small amounts of type-I rhamonogalacturonan regions. Its degree of methyl-esterification is approximately 62.4%. The effect of CKAP-2 on MDSC-medicated immunosuppression was primarily tested. CKAP-2 recovered the MSC2-supressed proliferation of CD4+ and CD8+ T-cells. This finding suggested that CKAP-2 can reverse MDSC-mediated T-cell suppression and that CKAP-2 can be potentially applied in antitumor therapy.

[Isolation, purification and characterization of antifungal protein from rice endophytic bacterim Bacillus subtilis G87].

OBJECTIVE: In order to obtain the antagonistic protein of Bacillus subtilis G87 and definitude its characterization. METHODS: Methods of ammonium sulfate precipitating and column chromatography analyzing were used to isolate and purify the protein. RESULTS: A purified protein (peak 6-2-1) was obtained which molecular weight was 50.8 kD by SDS-PAGE and isoelectric point was 5.90 by IEF-PAGE. The antifungal protein contained 0.62% saccharide and some proline or hydroxyproline, but no lipid and aromatic amino acid. The inhibitory activity of the antifungal protein would decreased distinctly at the higher temperature (> or = 60 degrees C) and in the condition of alkalinity (pH > 8), but tolerant to ultraviolet radiation, chloroform, trypsin, proteinase K and pepsin. CONCLUSION: Antifungal protein of Bacillus subtilis G87 was a kind of glycoprotein without aromatic hydrocarbon. It was sensitive to higher temperature and tight alkalinity but not to proteinase analog and ultraviolet radiation et al.

[Clinical study and electron microscope observation of tapeworm scolices on 548 cases of taeniasis treated with Binlang Chengqi Decoction].

OBJECTIVE: To observe the effect and mechanism of Chinese herbs in the treatment of taeniasis. METHODS: Five hundred and forty-eight cases of taeniasis were treated with Binlang Chengqi Decoction (BLCQD). The tapeworm scolices of ten cases were observed by electron microscope (EM). RESULTS: Among the 548 cases, 521 cases were cured and 27 cases were improved. The total effective rate was 100%. Foam-like secretion in the sucker of the tapeworm scolices and erosion of the epithelium in the cervical part were observed by scanning electron microscope. Observed by transmission electron microscope, the cortex was seriously damaged. The microvilli were exfoliated. The cells in the muscle layer and parenchyma layer were injured in various degrees. The mitochondria were tumefied or caved. And the nerve cord was damaged. CONCLUSION: BLCQD can not only paralyze the tapeworm scolex, but also injury the cells of the tapeworm scolex.