Proanthocyanidin-Driven Multifunctional Injectable Hydrogel as an Effective Skin Dressing for Atopic Dermatitis.

Patients with atopic dermatitis (AD) often experience symptoms of skin dryness, coinfection, oxidative damage, immune dysfunction, and inflammatory response. Clinical recommendations typically include antibiotics, glucocorticoids, and immunosuppressants, but frequent use of these medications can lead to drug resistance and adverse side effects. Herein, a pH/ROS-responsive injectable dual network hydrogel (HCFP) was developed by cross-linking oxidized hyaluronic acid, quaternized chitosan, and proanthocyanidins (PA) for the treatment of atopic dermatitis (AD).

Platycodon grandiflorus polysaccharides combined with hesperidin exerted the synergistic effect of relieving ulcerative colitis in mice by modulating PI3K/AKT and JAK2/STAT3 signaling pathways.

Ulcerative colitis (UC) is a chronic inflammatory disorder with a complex etiology, characterized by intestinal inflammation and barrier dysfunction. Platycodon grandiflorus polysaccharides (PGP), the primary component of Platycodon grandiflorus, and hesperidin (Hesp), a prominent active component in Citrus aurantium L. (CAL), have both demonstrated anti-inflammatory properties.

Fueling IgA-Dominated Humoral Immunity with an Intranasal Hybrid Tumor Vaccine to Opsonize and Strike Epithelial Breast Cancer.

Humoral immunity-cancer crosstalk has gained attention recently owing to its impact on tumor immune responses and therapy responsiveness. Here, it is shown that epithelial breast cancer cells can directly bind with non-antigen-specific IgA, dependent on polymeric immunoglobulin receptor (PIGR)-mediated transcytosis function, modulating tumoral inflammatory genes and sensitizing antitumor response. To harness this biology, a hybrid tumor vaccine is designed by covering the adjuvant-loaded cancer cell vesicles with a calcium phosphate shell, which retains the antigen information of the original tumor cells and exhibits robust mucosal adhesion in nasal tissues.

Inflammation-targeted nanomedicine prevents tumor metastasis following photodynamic therapy by reversing epithelial-mesenchymal transition and ROS-mediated immunosuppression.

Background: Prolonging the duration of photodynamic therapy (PDT) enhances the level of reactive oxygen species (ROS), thereby facilitating tumor ablation. However, our findings indicated that excessive ROS not only induces epithelial-mesenchymal transition (EMT) but also creates an immunosuppressive microenvironment in tumor, thereby triggering tumor metastasis.

Methods: We initially developed neutrophil membrane hybrid liposomes (NLs) that can specifically target inflamed tumor tissues following PDT.

Oncolytic polymer-mediated combretastatin A4 phosphate delivery for enhancing vascular disrupting therapy.

Although vascular disrupting agents (VDAs) can induce shutdown of blood flow and necrosis in the tumor core, eradicating tumor rim cells remains a significant challenge. Recently, researchers have developed various combination treatment strategies to improve the efficacy of VDAs. However, the aggravated hypoxic tumor microenvironment following vascular disruption limits the effectiveness of conventional therapeutic approaches.

Transforming tumors into 'high-risk bombs' triggers a neoantigen storm and amplifies immune responses.

Although various immunotherapies have improved the treatment of several challenging malignancies in clinical applications, current research suggests that neoantigens remain fundamental to the initiation of immunotherapy, implying a dependence on high mutation loads in tumors and stable target antigens. To overcome these limitations, we propose a novel immunotherapy paradigm that interferes with splicing to induce the expression of neoantigens and neoepitopes while simultaneously blocking autophagy to prevent their degradation through endogenous pathways. This approach ensures the stable expression and accumulation of neoantigens and neoepitopes in tumor cells.

Breaking-Down Tumoral Physical Barrier by Remotely Unwrapping Metal-Polyphenol-Packaged Hyaluronidase for Optimizing Photothermal/Photodynamic Therapy-Induced Immune Response.

The therapy of solid tumors is often hindered by the compact and rigid tumoral extracellular matrix (TECM). Precise reduction of TECM by hyaluronidase (HAase) in combination with nanotechnology is promising for solid tumor therapeutics, yet remains an enormous challenge. Inspired by the treatment of iron poisoning, here a remotely unwrapping strategy is proposed of metal-polyphenol-packaged HAase (named PPFH) by sequentially injecting PPFH and a clinically used iron-chelator deferoxamine (DFO).

Targeting Lysosome for Enhanced Cancer Photodynamic/Photothermal Therapy in a "One Stone Two Birds" Pattern.

Highly immunogenic programmed death of tumor cells, such as immunogenic cell death (ICD) and pyroptosis, strengthens antitumor responses and thus represents a promising target for cancer immunotherapy. However, the development of ICD and pyroptosis inducers remains challenging, and their efficiency is typically compromised by self-protective autophagy. Here, we report a potent ICD and pyroptosis-inducing strategy by coupling combined photodynamic/photothermal therapy (PTT/PDT) to biological processes in cancer cells.

Drug in Therapeutic Polymer: Sinomenine-Loaded Oxidation-Responsive Polymeric Nanoparticles for Rheumatoid Arthritis Treatment.

Rheumatoid arthritis (RA) is a chronic inflammatory joint disease that frequently involves cartilage damage and the destruction of the bone structure, ultimately resulting in disability and long-term pain. It is clear that overexpression of reactive oxygen species (ROS) and the complex inflammatory microenvironment are the main causes of RA pathogenesis; thereby, the efficacy of any single-drug treatment is limited. Herein, we formulated a therapeutic hyaluronic acid derivative (PAM-HA) with adsorption capacity to the subchondral bone, a long retention time within inflamed joints, and ROS-scavenging capacity, which was used as a drug carrier for realizing the controlled release of sinomenine (Sin) within arthritic joints.

Platycodon grandiflorus polysaccharide regulates colonic immunity through mesenteric lymphatic circulation to attenuate ulcerative colitis.

Platycodon grandiflorus polysaccharide (PGP) is one of the main components of P. grandiflorus, but the mechanism of its anti-inflammatory effect has not been fully elucidated. The aim of this study was to evaluate the therapeutic effect of PGP on mice with dextran sodium sulfate (DSS)-induced ulcerative colitis (UC) and explore the underlying mechanisms.

Engineering mitochondrial uncoupler synergistic photodynamic nanoplatform to harness immunostimulatory pro-death autophagy/mitophagy.

Generally, autophagy/mitophagy, as a highly conserved lysosomal-based catabolic pathway, compromises the photodynamic therapy (PDT) efficiency by increasing the adaptation of tumor cells toward reactive oxygen species (ROS)-triggered protein damages and mitochondrial destruction. On the other hand, excessively activated autophagy/mitophagy cascades can provoke autophagic cell death and promote the endogenous antigens release of dying cells, thus playing a vital role in initiating the antitumor immune responses. To harness the exquisite immunomodulating effect of pro-death autophagy/mitophagy, we rationally constructed a MnO shell-coated multifunctional porphyrinic metal-organic framework (MOF) to load carbonyl cyanide 3-chlorophenylhydrazone (CCCP).

Engineering a curcumol-loaded porphyrinic metal-organic framework for enhanced cancer photodynamic therapy.

Photodynamic therapy (PDT), a non-invasive and safe treatment, is a clinical promising alternative strategy for certain cancers. Although PDT can trigger tumor specific immunity, the immunosuppressive tumor microenvironment severely limits the efficacy of photodynamic immunotherapy. Curcumol (CUR), extracted from essential oils of traditional Chinese medicine, has potential immune activation effect for cancer immunotherapy.

Heparin-Coated Photosensitive Metal-Organic Frameworks as Drug Delivery Nanoplatforms of Autophagy Inhibitors for Sensitized Photodynamic Therapy against Breast Cancer.

Photosensitive nanosized metal-organic frameworks (nanoMOFs) with a tunable structure and high porosity have been developed recently as nanophotosensitizers (nanoPSs) for photodynamic therapy (PDT). However, the effect of photodynamic therapy is greatly limited by the fast blood clearance and poor tumor retention of the ordinary nanoPSs. Besides, autophagy, a prosurvival self-cannibalization pathway mediated by autolysosomes, was elevated by cytotoxic reactive oxygen species (ROS) produced during PDT.

Metabolic engineering of Escherichia coli for efficient osmotic stress-free production of compatible solute hydroxyectoine.

Compatible solutes are key for the ability of halophilic bacteria to resist high osmotic stress. They have received wide attention from researchers for their excellent osmotic protection properties. Hydroxyectoine is a particularly important compatible solute, but its production by microbes faces several challenges, including low titer/yield, the presence of the byproduct ectoine, and the requirement of high salinity.

CRISPRi-Based Dynamic Control of Carbon Flow for Efficient -Acetyl Glucosamine Production and Its Metabolomic Effects in .

Carbon competition between cell growth and product synthesis is the bottleneck in efficient -acetyl glucosamine (GlcNAc) production in microbial cell factories. In this study, a xylose-induced T7 RNA polymerase-P promoter system was introduced in W3110 to control the GlcNAc synthesis. Meanwhile, an arabinose-induced CRISPR interference (CRISPRi) system was applied to adjust cell growth by attenuating the transcription of key growth-related genes.

Observation of the clinical effect of the combined therapy of zushima tablet and western medicine in the treatment of rheumatoid arthritis and MRI test results.

To evaluate the clinical efficacy of combined therapy of Zushima tablet and western medicine in treatment of rheumatoid arthritis and analyze the MRI test results. A total of 170 patients who had been treated for rheumatoid arthritis at our hospital from August 2016 and June 2018, were enrolled as research objects. They were randomly divided into control group and research group, with 85 patients in each group.