A Photo-induced Cross-Linking Enhanced A and B Combined Multi-Functional Spray Hydrogel Instantly Protects and Promotes of Irregular Dynamic Wound Healing.

Wounds in harsh environments can face long-term inflammation and persistent infection, which can slow healing. Wound spray is a product that can be rapidly applied to large and irregularly dynamic wounds, and can quickly form a protective film in situ to inhibit external environmental infection. In this study, a biodegradable A and B combined multi-functional spray hydrogel is developed with methacrylate-modified chitosan (CSMA1st) and ferulic acid (FA) as type A raw materials and oxidized Bletilla striata polysaccharide (OBSP) as type B raw materials. The precursor CSMA1st-FA/OBSP (CSOB-FA1st) hydrogel is formed by the self-cross-linking of dynamic Schiff base bonds, the CSMA-FA/OBSP (CSOB-FA) hydrogel is formed quickly after UV-vis light, so that the hydrogel fits with the wound. Rapid spraying and curing provide sufficient flexibility and rapidity for wounds and the hydrogel has good injectability, adhesive, and mechanical strength. In rats and miniature pigs, the A and B combined spray hydrogel can shrink wounds and promote healing of infected wounds, and promote the enrichment of fibrocyte populations. Therefore, the multifunctional spray hydrogel combined with A and B can protect irregular dynamic wounds, prevent wound infection and secondary injury, and be used for safe and effective wound treatment, which has a good prospect for development.

Preparation of Oral Core-Shell Zein Nanoparticles to Improve the Bioavailability of Glycyrrhizic Acid for the Treatment of Ulcerative Colitis.

In this study, oral colon-targeted adhesion core-shell nanoparticles were designed by applying FA-Zein as the core and using pectin as the shell to enhance the low bioavailability exhibited by glycyrrhizic acid (GA) and the anti-inflammatory effect in specific parts of the intestine. As indicated by the results, the nanoparticles (NPs) remained stable in the stomach and small intestine, while pectins began to degrade and release GA in considerable amounts in the colon with the abundant flora. Subsequently, folate-acid targeting was further assessed with Raw 264.7 and NCM 460 cells. Lastly, NPs were reported to exhibit high adhesion on the colon by using the DSS-induced ulcerative colitis mouse model. Moreover, as indicated by in vitro and in vivo studies, nanoparticles could decrease the levels of MPO and TNF-α by reducing macrophages and neutrophils. In brief, this study provides an ideal loaded natural anti-inflammatory drug delivery system to treat ulcerative colitis.

Xanthotoxin (8-methoxypsoralen): A review of its chemistry, pharmacology, pharmacokinetics, and toxicity.

Xanthotoxin (XAT) is a natural furanocoumarins, a bioactive psoralen isolated from the fruit of the Rutaceae plant Pepper, which has received increasing attention in recent years due to its wide source and low cost. By collecting and compiling literature on XAT, the results show that XAT exhibits significant activity in the treatment of various diseases, including neuroprotection, skin repair, osteoprotection, organ protection, anticancer, antiinflammatory, antioxidative stress and antibacterial. In this paper, we review the pharmacological activity and potential molecular mechanisms of XAT for the treatment of related diseases. The data suggest that XAT can mechanistically induce ROS production and promote apoptosis through mitochondrial or endoplasmic reticulum pathways, regulate NF-κB, MAPK, JAK/STAT, Nrf2/HO-1, MAPK, AKT/mTOR, and ERK1/2 signaling pathways to exert pharmacological effects. In addition, the pharmacokinetics properties and toxicity of XAT are discussed in this paper, further elucidating the relationship between structure and efficacy. It is worth noting that data from clinical studies of XAT are still scarce, limiting the use of XAT in the clinic, and in the future, more in-depth studies are needed to determine the clinical efficacy of XAT.

H-Bonds Enhanced Natural Polyphenols Bined Polysaccharide/Gelatin Composites with Controlled Photothermal Stimulation Phase Transition for Wound Care.

Severe open wounds should be closed immediately and regularly undergo re-examination and debridement. Therefore, dressings should effectively cover the wound, creating a moist environment for healing while meeting mechanical requirements for daily movement and adaptability. Herein, a low-cost and easy-to-prepare plant polysaccharide hydrogel was reported. The Mesona chinensis Benth polysaccharide strengthened the hydrogel network by hydrogen bonding and changed the phase transition temperature, but retained the thermal response characteristics of the hydrogel. By adjusting the polysaccharide concentration, MepGel(1) can be prepared to remain stable as a semisolid at body temperature and transform into a shear-thinning semifluid state when appropriately heated. The composite hydrogel could be easily shaped, effectively closing wounds of different shapes, while maintaining excellent mechanical properties. Importantly, this composite hydrogel had a near-infrared photothermal effect resulting in excellent antibacterial effect and collided with its own thermal response producing functions conducive to wound care, like accelerating the self-healing of the dressing, achieving re-adhesion, and further covering the wound. Furthermore, the hydrogel had excellent biocompatibility, enhancing immunity and promoting healing of bacterial-infected wounds. The low cost and rich functionality demonstrated by MepGel had the potential to face the enormous challenges and economic burden of clinical wound healing.

Biocompatible and biodegradable Bletilla striata polysaccharides hydrogels crosslinked by BDDE for wound healing through the regulating of macrophage polarization.

Bletilla striata polysaccharide (BSP) is a naturally occurring polysaccharide that demonstrates notable biocompatibility and biodegradability. Additionally, BSP possesses therapeutic attributes, including anti-inflammatory and reparative actions. Herein, we report a novel BSP hydrogel prepared using 1,4-butanediol diglycidyl ether (BDDE) as a cross-linking agent. The hydrogel was synthesized via condensation of the hydroxyl group in the BSP molecule with the epoxy group in BDDE. This technique of preparation preserves BSP's natural properties while avoiding any potentially hazardous or adverse effects that may occur during the chemical alteration. Compared with BSP before crosslinking, BSP hydrogel has distinct advantages, such as a three-dimensional network structure, improved water retention, enhanced swelling capacity, greater thermal stability, and superior mechanical properties. Experiments on in vitro cytotoxicity, hemolysis, and degradation revealed that BSP hydrogel had good biocompatibility and biodegradability. Finally, we evaluated the in vivo wound repair effect of BSP hydrogel, and the results showed that BSP hydrogel had a significant wound-healing effect. Furthermore, the BSP hydrogel promoted the polarization of M1-type macrophages towards the M2-type and reduced the inflammatory response during the wound healing phase. Because of its ease of production, safety, efficacy, and environmental friendliness, BSP hydrogel is considered a highly promising material for wound dressings.

Mucoadhesive and thermosensitive Bletilla striata polysaccharide/chitosan hydrogel loaded nanoparticles for rectal drug delivery in ulcerative colitis.

Ulcerative colitis (UC) is a chronic disease with diffuse mucosal inflammation limited to the colon. A topical drug delivery system that could be facilely performed and efficiently retained at colon are attractive for clinical ulcerative colitis treatment. Herein, a novel platform for rectal administration of thermosensitive hydrogel co-loaded with nanoparticles to treat ulcerative colitis was developed. Thiolated-hyaluronic acid was synthesized, and prepared nanoparticles with zein and Puerarin. And the Bletilla striata polysaccharide with colonic mucosa repair effect was oxidized, and mixed with chitosan and ß-sodium glycerophosphate to prepare thermosensitive hydrogel. Thermosensitive hydrogels were combined with nanoparticles to investigate their mucosal adhesion, retention, and permeability, as well as their therapeutic effects on ulcerative colitis. Thiolated-hyaluronic acid nanoparticles had good stability, and could be quickly converted into hydrogel at body temperature when combined with thermosensitive hydrogel. The nanoparticles-loaded thermosensitive hydrogel also was excellent at mucosal penetration, enhancing the retention time of drugs in colon, and effectively controlling drug release. In vivo ulcerative colitis treatment revealed that the nanoparticles-loaded hydrogel significantly repaired the colonic mucosa and inhibit colonic inflammation. Therefore, the thermosensitive hydrogel co-loaded nanoparticles will have a promising application in effective treatment of ulcerative colitis by topical administration.

Extraction and characterization of chitosan from Eupolyphaga sinensis Walker and its application in the preparation of electrospinning nanofiber membranes.

Due to its capabilities for wound healing, antimicrobial defense, hemostasis, and biodegradation, chitosan has seen increased use in biomedical disciplines in recent years. In the meantime, efforts have been made to develop and use insect chitosan as a source to address the seasonal, irritating, and regional shortcomings of traditional shrimp and crab chitosan. In this study, a new type of insect chitosan (DCS) was first extracted from Eupolyphaga sinensis Walker by a low-temperature intermittent method and was compared with commercially available pharmaceutical chitosan (CS). Firstly, the degree of deacetylation and molecular weight of DCS were determined, and DCS was characterized by FT-IR, 1H NMR, XRD, and TGA-DTG. On this basis, DCS was mixed with PVA and PEO to create a novel electrospun nanofiber membrane. The air permeability, antibacterial properties, and biocompatibility of the nanofiber membrane were evaluated, as well as the membrane's shape, structure, and mechanical characteristics. Finally, the activity of nanofiber membranes in promoting wound healing was verified with a rat full-thickness skin defect model, hoping to provide a reference for the development of new drug delivery carriers and wound dressings.

Physical dual-network photothermal antibacterial multifunctional hydrogel adhesive for wound healing of drug-resistant bacterial infections synthesized from natural polysaccharides.

Wound-healing of drug-resistant bacterial infections has always been a clinical challenge. The design and development of effective and economically safe wound dressings with antimicrobial activity and healing-promoting properties is highly desirable, especially in the context of wound-infections. Herein, we designed a physical dual-network multifunctional hydrogel adhesive based on polysaccharide material for the treatment of full-thickness skin defects infected with multidrug-resistant bacteria. The hydrogel utilized ureido-pyrimidinone (UPy)-modified Bletilla striata polysaccharide (BSP) as the first physical interpenetrating network for providing some brittleness and rigidity; and then branched macromolecules formed after cross-linking Fe3+ with dopamine-conjugated di-aldehyde-hyaluronic acid as the second physical interpenetrating network for providing some flexibility and elasticity. In this system, BSP and hyaluronic acid (HA) are used as synthetic matrix materials to provide strong biocompatibility and wound-healing ability. In addition, ligand cross-linking of catechol-Fe3+ and quadrupole hydrogen-bonding cross-linking of UPy-dimer can form a highly dynamic physical dual-network structure, which imparts good rapid self-healing, injectability, shape-adaptation, NIR/pH responsiveness, high tissue-adhesion and mechanical properties of this hydrogel. Meanwhile, bioactivity experiments demonstrated that the hydrogel also possesses powerful antioxidant, hemostatic, photothermal-antibacterial and wound-healing effects. In conclusion, this functionalized hydrogel is a promising candidate for clinical treatment of full-thickness bacteria-stained wound dressing materials.

Fabrication and characterization of PVA@PLA electrospinning nanofibers embedded with Bletilla striata polysaccharide and Rosmarinic acid to promote wound healing.

In this study, a novel nanofiber material with Polylactic acid (PLA), natural plant polysaccharides-Bletilla striata polysaccharide (BSP) and Rosmarinic acid (RA) as the raw materials to facilitate wound healing was well prepared through coaxial electrospinning. The morphology of RA-BSP-PVA@PLA nanofibers was characterized through scanning electron microscopy (SEM), and the successful formation of core-shell structure was verified under confocal laser microscopy (CLSM) and Fourier transform infrared spectroscopy (FTIR). RA-BSP-PVA@PLA exhibited suitable air permeability for wound healing, as indicated by the result of the water vapor permeability (WVTR) study. The results of tension test results indicated the RA-BSP-PVA@PLA nanofiber exhibited excellent flexibility and better accommodates wounds. Moreover, the biocompatibility of RA-BSP-PVA@PLA was examined through MTT assay. Lastly, RA-BSP-PVA@PLA nanofibers can induce wound tissue growth, as verified by the rat dorsal skin wound models and tissue sections. Furthermore, RA-BSP-PVA@PLA can facilitate the proliferation and transformation of early wound macrophages, and down-regulate MPO+ expression of on the wound, thus facilitating wound healing, as confirmed by the result of immunohistochemical. Thus, RA-BSP-PVA@PLA nanofibers show great potential as wound dressings in wound healing.

Advances in Formulations of Microneedle System for Rheumatoid Arthritis Treatment.

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic joint inflammation, eventually leading to severe disability and premature death. At present, the treatment of RA is mainly to reduce inflammation, swelling, and pain. Commonly used drugs are non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, and disease-modifying anti-rheumatic drugs (DMARDs). These drugs lack specificity and require long-term, high-dose administration, which can cause serious adverse effects. In addition, the oral, intravenous, and intra-articular injections will reduce patient compliance, resulting in high cost and low bioavailability. Due to these limitations, microneedles (MNs) have emerged as a new strategy to efficiently localize the drugs in inflamed joints for the treatment of RA. MNs can overcome the cuticle barrier of the skin without stimulating nerves and blood vessels. Which can increase patient compliance, improve bioavailability, and avoid systemic circulation. This review summarizes and evaluates the application of MNs in RA, especially dissolving MNs (DMNs). We encourage the use of MNs to treat RA, by describing the general properties of MNs, materials, preparation technology, drug release mechanism, and advantages. Furthermore, we discussed the biological safety, development prospects, and future challenges of MNs, hoping to provide a new strategy for the treatment of RA.

Ser-2030, but not Ser-2808, is the major phosphorylation site in cardiac ryanodine receptors responding to protein kinase A activation upon beta-adrenergic stimulation in normal and failing hearts.

We have recently shown that RyR2 (cardiac ryanodine receptor) is phosphorylated by PKA (protein kinase A/cAMP-dependent protein kinase) at two major sites, Ser-2030 and Ser-2808. In the present study, we examined the properties and physiological relevance of phosphorylation of these two sites. Using site- and phospho-specific antibodies, we demonstrated that Ser-2030 of both recombinant and native RyR2 from a number of species was phosphorylated by PKA, indicating that Ser-2030 is a highly conserved PKA site. Furthermore, we found that the phosphorylation of Ser-2030 responded to isoproterenol (isoprenaline) stimulation in rat cardiac myocytes in a concentration- and time-dependent manner, whereas Ser-2808 was already substantially phosphorylated before beta-adrenergic stimulation, and the extent of the increase in Ser-2808 phosphorylation after beta-adrenergic stimulation was much less than that for Ser-2030. Interestingly, the isoproterenol-induced phosphorylation of Ser-2030, but not of Ser-2808, was markedly inhibited by PKI, a specific inhibitor of PKA. The basal phosphorylation of Ser-2808 was also insensitive to PKA inhibition. Moreover, Ser-2808, but not Ser-2030, was stoichiometrically phosphorylated by PKG (protein kinase G). In addition, we found no significant phosphorylation of RyR2 at the Ser-2030 PKA site in failing rat hearts. Importantly, isoproterenol stimulation markedly increased the phosphorylation of Ser-2030, but not of Ser-2808, in failing rat hearts. Taken together, these observations indicate that Ser-2030, but not Ser-2808, is the major PKA phosphorylation site in RyR2 responding to PKA activation upon beta-adrenergic stimulation in both normal and failing hearts, and that RyR2 is not hyperphosphorylated by PKA in heart failure. Our results also suggest that phosphorylation of RyR2 at Ser-2030 may be an important event associated with altered Ca2+ handling and cardiac arrhythmia that is commonly observed in heart failure upon beta-adrenergic stimulation.

[Effect of Cr(VI) stress on growth of three herbaceous plants and their Cr uptake].

In order to elucidate the toxic mechanisms of Trifolium repens, Festuca arundinacea and Medicago sativa under chromium [Cr (VI)] stress, provide a theoretic foundation for phytoremediation of Cr-contaminated soil, pot experiment was conducted to investigate the effects of Cr(VI) on plant growth, physiological characteristics, Cr accumulation and distribution in three herbaceous plants. Soil sample was treated by adding K2Cr2O7 with the Cr(VI) concentration of 0, 100, 200, 300 and 400 mg x kg(-1), respectively. The results indicated that the average tolerance indices of T. repens, F. arundinacea and M. sativa were 62.5, 48.3 and 36.33, respectively. Compared with control group, contents of chlorophyll, the activity of superoxide dismutase(SOD) and peroxidase (POD) were 57.14%, 51.51%, 35.76% and 63.27%, 52.96%, 41.36% in T. repens, and F. arundinacea, respectively, but M. sativa died in 400 mg x kg(-1) Cr(VI) treatment. The plant height, root length, dry mass of roots and shoots decreased under Cr(VI) stress in three herbaceous plants, and M. sativa > F. arundinacea > T. repens, however, the content of malonyldialdehyde (MDA) increased compared to the control, and the variation range of M. sativa was the highest, while T. repens was the smallest among them. The tolerance of Cr( VI) was T. repens > F. arundinacea > M. sativa. Cr mainly distributed in cell wall and then in the cytoplasm, and less distributed in the mitochondrion and chloroplast in leaves of three herbaceous plants, whereas the content of chlorophyll, MDA, the activity of SOD and POD correlated well with Cr accumulation in the mitochondrion and chloroplast. Cr concentration in the subcellular of leaves increased with the adding Cr(VI) concentration,and M. sativa > F. arundinacea > T. repens. In comparison with T. repens, F. arundinacea, Cr concentration in the leaves of M. sativa was the maximal, i.e. 51.44 mg x kg(-1), and the proportions in the mitochondrion (18.04%) and chloroplast (19.09%) were also higher in 300 mg x kg(-1) Cr(VI). The average accumulation factors of shoots/roots were 1.22/1.54, 1.16/1.44 and 1.26/1.62, while the average translocation factors were 0.78, 0.78 and 0.74 in T. repens, F. arundinacea and M. sativa, respectively. The results suggest that T. repens and F. arundinacea are promising for the phytoremediation of Cr-contaminated soil.