Bilayer Scaffold for Corneal Stromal Engineering: Solvent-Cast Polyvinyl Alcohol/Sodium Alginate and Electrospun Aligned Polycaprolactone Fibers.
Authors: Orash Mahmoudsalehi A, Rios KSC, Guerrero-Beltrán CE, Ortega-Lara W
Journal: Polymers
depression treatment
mental health
open access
Abstract
Ulcerative colitis (UC) is characterized by persistent inflammation of the colonic mucosa []. Epidemiological data indicate that UC has its highest prevalence in Western industrialized countries, particularly in Norway and the United States, with a global prevalence estimated at approximately 5 million cases as of 2023 []. UC poses significant socioeconomic challenges, with annual costs-both direct and indirect-ranging from $8.1 to $14.9 billion in the United States alone []. The current management of UC is primarily pharmacological, involving agents such as 5-aminosalicylic acid (5-ASA), corticosteroids, and thiopurines. Surgical intervention may be necessary for patients who do not respond to medical therapy [,]. However, these treatments primarily offer symptomatic relief and are often associated with adverse effects, including gastrointestinal disturbances, opportunistic infections, and hepatotoxicity []. Consequently, there is an urgent need for the development of novel therapeutic strategies for UC that prioritize efficacy, safety, and cost-effectiveness. Aconite is derived from the lateral roots of Debx., and is commonly used as an herb and dietary supplement [,]. Although aconite is not traditionally prescribed for colitis, classical Chinese medical literature highlights its therapeutic potential for UC. For instance, the Compendium of Materia Medica (Ben Cao Gang Mu) notes its efficacy in “managing chronic dysentery and spleen diarrhea”, while the Complete Records of Holy Universal Relief (Shengji Zonglu) details the use of aconite pills for “intermittent dysentery and red-white dysentery”. Contemporary pharmacological research has demonstrated that aconite possesses a range of bioactivities, most notably potential benefits for UC management []. Historically, the alkaloids in aconite were considered its active components, whereas aconite polysaccharides (APs) were often regarded as ineffective, resulting in considerable resource wastage. However, recent studies have identified polysaccharides as a promising therapeutic option for UC due to their high safety profile and significant biological effects []. APs have recently been recognized as bioactive constituents of aconite []. Research has revealed that APs exhibit a remarkable immunomodulatory effect, as they are capable of mitigating the reduction in thymic and splenic indices and enhancing CD4 T lymphocyte differentiation in immunocompromised mice []. Additionally, APs markedly alleviate rhubarb-induced diarrhea in rats, indicating potential gastrointestinal regulatory properties []. Hence, it was hypothesized that APs may possess therapeutic potential for improving UC. To facilitate the future development and application of APs, it is essential to analyze their chemical characteristics and verify their efficacy in ameliorating UC. In mammals, intestinal homeostasis is collectively maintained by the gut microbiota (GM), the mucus barrier (primarily composed of mucins, antimicrobial peptides, etc.), the physical barrier (epithelial cells, etc.), and the immune barrier (mainly comprising immune cells, cytokines, etc.) []. Notably, GM plays a pivotal role in mucus layer formation, the integrity of the physical barrier, and dynamic equilibrium of the immune barrier []. Disruption of GM caused by environmental or genetic factors results in intestinal homeostasis imbalance, ultimately resulting in UC []. Therapeutic interventions, including pharmacological agents, dietary intervention, and fecal microbiota transplantation (FMT), exert UC-alleviating effects by modulating GM to restore mucus, physical, and immune barrier functions [, , ]. GM is a key focus for elucidating the mechanism by which APs improves UC. Gastrointestinal digestion minimally degrades natural polysaccharides []. Most polysaccharides can reach the intestine and interact with GM: the GM metabolizes polysaccharides into bioactive molecules (e.g., short-chain fatty acids), while polysaccharides reciprocally regulate GM []. APs have demonstrated their regulatory effects on GM. Specifically, APs enriches , and in the feces of immunosuppressed mice, while elevating levels of microbial metabolites, including butyrate, acetate, and propionate []. However, whether APs can improve UC by regulating GM is still unclear. Given GM's influence on UC progression and its interaction with polysaccharides, APs may alleviate UC by modulating GM.