Lin Wang

Background: Ulcerative colitis (UC) is an inflammatory disease of the colon that is characterized by mucosal ulcers. Given its increasing prevalence worldwide, it is imperative to develop safe and effective drugs for treating UC. Emodin, a natural anthraquinone derivative present in various medicinal herbs, has demonstrated therapeutic effects against UC. However, low bioavailability due to poor water solubility limits its clinical applications. Methods: Emodin-borate nanoparticles (EmB) were synthesized to improve drug solubility, and they modified with oligomeric mannitol into microgels (EmB-MO) for targeted delivery to intestinal macrophages that express mannose receptors. UC was induced in a mouse model using dextran sulfate sodium (DSS), and different drug formulations were administered to the mice via drinking water. The levels of inflammation-related factors in the colon tissues and fecal matter were measured using enzyme-linked immunosorbent assay. Intestinal permeability was evaluated using fluorescein isothiocyanate dextran. HE staining, in vivo imaging, real-time PCR, and western blotting were performed to assess intestinal barrier dysfunction. Results: Both EmB and EmB-MO markedly alleviated the symptoms of UC, including body weight loss, stool inconsistency, and bloody stools and restored the levels of pro- and anti-inflammatory cytokines. However, the therapeutic effects of EmB-MO on the macroscopic and immunological indices were stronger than those of EmB and similar to those of 5-aminosalicylic acid. Furthermore, EmB-MO selectively accumulated in the inflamed colon epithelium and restored the levels of the gut barrier proteins such as ZO-1 and Occludin. Conclusions: EmB-MO encapsulation significantly improved water solubility, which translated to greater therapeutic effects on the immune balance and gut barrier function in mice with DSS-induced UC. Our findings provide novel insights into developing emodin-derived drugs for the management of UC.

Graphene oxide (GO) has arisen as an effective adsorbent for water treatment owing to its high removal efficiency for water pollutants. However, separating GO adsorbents from the pollutant solution is difficult after adsorption. The GO adsorbents are unsuitable for various dyes, and can only remove cationic dyes from an aqueous solution. To address these issues, this study utilized a simple and cost-effective layer-by-layer assembly technique to deposit multilayer films onto solid substrates. These films were composed of poly(allylamine hydrochloride)–dextran (PAHD) microgels and GO, and were designed to be highly effective while remaining affordable. The PAHD/GO multilayer films obtained produced an effortless separation process and demonstrated exceptional adsorption capabilities for cationic, anionic and non-ionic dyes. Specifically, the adsorption capacities for carmine and mulberry red were notably high, measuring 337.4 and 417.7 mg g-1, respectively. In addition, the PAHD/GO multilayer films could be regenerated well in sodium chloride solution without obvious compromise of removal efficiency. The adsorption kinetics, isotherms and thermodynamics of dyes on the PAHD/GO multilayer films were also studied. Thanks to the straightforward manufacturing process and outstanding adsorption capabilities of PAHD/GO multilayer films, this study presents a significant opportunity to advance the practical application of GO in water treatment.

Background Ulcerative colitis (UC) is an inflammatory disease of the colon that is characterized by mucosal ulcers. Given its increasing prevalence worldwide, it is imperative to develop safe and effective drugs for treating UC. Emodin, a natural anthraquinone derivative presenting in various medicinal herbs, has demonstrated therapeutic effects against colitis. However, low bioavailability due to poor water solubility limits its clinical applications. Methods Emodin-borate nanoparticles (EmB) were synthesized to improve drug solubility, and modified with oligomeric mannitol into microgels (EmB-MO) for targeted delivery to intestinal cells expressing mannose receptors. Colitis was induced in a mouse model using dextran sulphate sodium (DSS), and the different drug formulations were administered to the mice via drinking water. The levels of inflammation-related factors in the colon tissues and fecal matter were measured by enzyme linked immunosorbent assay (ELISA). Intestinal permeability was evaluated using fluorescein isothiocyanate dextran. HE staining, in vivo imaging, real-time PCR and western blotting were performed to assess intestinal barrier dysfunction. Results Both EmB and EmB-MO markedly alleviated the symptoms of colitis, including body weight loss, stool inconsistency and bloody stools, and restored the levels of pro- and anti-inflammatory cytokines. However, the therapeutic effects of EmB-MO on the macroscopic and immunological indices were stronger compared to that of EmB, and similar to that of 5-aminosalicylicacid. Furthermore, EmB-MO selectively accumulated in the inflamed colon epithelium, and restored the levels of the gut barrier proteins ZO-1 and occludin. Conclusions Encapsulation of EmB-MO significantly improved water solubility, which translated to greater therapeutic effects on the immune balance and gut barrier function in mice with DSS-induced colitis. Our findings provide novel insights into developing emodin-derived drugs for the management of UC.

Manganese-zinc ferrite (MZF) is known as high-performance magnetic material and has been used in many fields and development. In the biomedical applications, the biocompatible MZF formulation attracted much attention. In this study, water-soluble amphiphilic vitamin E (TPGS, d-alpha-tocopheryl poly(ethylene glycol 1000) succinate) formulated MZF nanoparticles were synthesized to serve as both a magnetic resonance imaging (MRI) contrast agent and a vehicle for creating magnetically induced hyperthermia against cancer. The MZF nanoparticles were synthesized from a metallic acetylacetonate in an organic phase and further modified with TPGS using an emulsion and solvent-evaporation method. The resulting TPGS-modified MZF nanoparticles exhibited a dual-contrast ability, with a longitudinal relaxivity (35.22 s⁻¹ mM Fe⁻¹) and transverse relaxivity (237.94 s⁻¹ mM Fe⁻¹) that were both higher than Resovist^®. Furthermore, the TPGS-assisted MZF formulation can be used for hyperthermia treatment to successfully suppress cell viability and tumor growth after applying an alternating current (AC) electromagnetic field at lower amplitude. Thus, the TPGS-assisted MZF theranostics can not only be applied as a potential contrast agent for MRI but also has potential for use in hyperthermia treatments.

This study demonstrated both adipose‐derived stem cells (ASCs) in vitro and in vivo combined with three‐dimensional (3D) porous sponge matrices on implant wound healing. Sponge matrices were created from hyaluronic acid (HA), collagen (Col), and gelatin (Gel), constructing two types: HA‐L (low content) and HA‐H (high content), to be cross‐linked with 1‐ethyl‐3‐(3‐dimethylaminopropyl) carbodiimide (EDC). Fourier transform infrared spectroscopy method verified carboxyl groups of HA and amino groups of Col and Gel reacting between the raw materials and scaffolds to identify the successive cross‐linking. The swelling ratios of two types of sponge matrices were analyzed by water absorption capabilities, and the results displayed both over 30‐fold dry scaffold weight enhancements. In biodegradation tests, matrices were hydrolyzed over time by three cutaneous enzymes, hyaluronidase, lysozyme, and collagenase I. ASCs from rats were cultured within the HA‐H scaffold, demonstrating higher antioxidative abilities and secretions on related genes and proteins compared to the other two groups. The ASC HA‐H matrix promoted cell proliferation to stimulate capillary angiogenesis inducer secretions, including vascular endothelial growth factor (VEGF) and transforming growth factor‐β (TGF‐β). In vivo histological examinations showed ASCs from implanted HA‐H implant transported into the subcutis, and rat skin cells also infiltrated into the original matrix zone to increase the extracellular matrix (ECM) reconstructions. Our experimental data revealed that the ASC HA‐H sponge implant was effective in improving wound repair.

Melanoma is an aggressive cancer with high lethality. In order to find new anticancer agents, isokotomolide A (Iso A) and secokotomolide A (Sec A) isolated from Cinnamomum kotoense were identified to be potential bioactive agents against human melanoma but without strong antioxidative properties. Cell proliferation assay displayed Iso A and Sec A treated in the normal human skin cells showed high viabilities. It also verified that two of them possess strong antimelanoma effect in concentration-dependent manners, especially on B16F10, A2058, MeWo, and A375 cells. Wound healing assay presented their excellent antimigratory effects. Through 3-N,3-N,6-N,6-N-Tetramethylacridine-3,6-diamine (acridine orange, AO) staining and Western blot, the autophagy induced by treatment was confirmed, including autophagy-related proteins (Atgs). By using annexin V–FITC/PI double-stain, the apoptosis was confirmed, and both components also triggered the cell cycle arrest and DNA damage. We demonstrated the correlations between the mitogen-activated protein kinase (MAPK) pathway and antimelanoma, such as caspase cascade activations. To further evaluate in vivo experiments, the inhibition of tumor cell growth was verified through the histopathological staining in a xenograft model. In this study, it was confirmed that Iso A and Sec A can encourage melanoma cell death via early autophagy and late apoptosis processes.