RAW264.7 (小鼠单核巨噬细胞白血病细胞)（STR鉴定）

Inflammatory bowel disease (IBD) management is often hindered by limited efficacy and significant systemic side effects of traditional oral medications, owing to their lack of targeted delivery and multifunctional capabilities. This study introduces a novel orally sequence-targeted delivery system, QT-CMOF@HAS nanocube, based on hydrophobic cross-linked CD-MOF (CMOF) for the precise delivery of quercetin (Qu) to the inflamed colonic lesions. To enhance the mitochondrial targeting capabilities of Qu, a mitochondrial-functionalized Qu-(5-carboxypentyl) (triphenyl) phosphonium bromide (TPP) precursor complex (QT) was initially synthesized and loaded into the CMOF. A chitosan/glutathione-responsive hyaluronic acid (HAS) shell was subsequently coated onto the CMOF, forming the QT-CMOF@HAS nanoplatform to further enhance the gastrointestinal tolerance. Our results demonstrated that QT-CMOF@HAS significantly alleviated colitis symptoms by modulating the repolarization of pro-inflammatory M1 macrophages to anti-inflammatory M2 phenotypes and deactivation of the TLR4/MyD88/NF-κB pathway, thus reducing the production of inflammatory cytokines. Furthermore, the integrity of the intestinal mucosal barrier and the gut microbiota were enhanced. This study highlights the potential of QT-CMOF@HAS nanocube as a promising therapeutic tool for IBD treatment, offering a multifaceted approach to tackle inflammation and support mucosal healing in a targeted and controlled manner.

M1 macrophage polarization plays a key role in the onset and progression of sepsis. Fibroblast growth factor 15 (FGF15) suppresses septic inflammation through its FGF receptor 4 (FGFR4); however, the underlying mechanisms are largely unclear. In this study, we evaluated the anti-inflammatory effects of recombinant FGF15 (rFGF15) in cecal ligation and puncture (CLP)-induced septic mice in vivo, as well as lipopolysaccharide (LPS)-stimulated mouse bone marrow-derived macrophages (BMDMs) and RAW264.7 macrophages in vitro. We observed that rFGF15 suppressed M1 macrophage polarization and associated inflammatory responses in both CLP-induced septic mice and LPS-stimulated BMDMs and RAW264.7 macrophages. Additionally, macrophage-depleted CLP mice transplanted with LPS-stimulated BMDMs pre-treated with rFGF15 exhibited reduced multi-organ inflammation and enhanced survival compared to those receiving LPS-stimulated BMDMs without rFGF15 treatment. Mechanistically, FGF15 activated the neurofibromin 2 (NF2)-Hippo pathway through FGFR4, leading to the inhibition of glycolysis, lactate production, and histone H3K18 lactylation. This led to reduced expression of interferon regulatory factor 7 (Irf7), a key regulator of type I interferon responses. In conclusion, FGF15 suppresses M1 macrophage polarization and associated inflammatory responses in sepsis by activating the NF2-Hippo pathway, thereby inhibiting H3K18 lactylation-driven Irf7 expression. FGF15 holds promise as a potential innovative therapy for sepsis.

Excessive reactive oxygen species (ROS) is a hallmark of both the onset and progression of inflammatory bowel disease (IBD), where a continuous cycle of ROS and inflammation drives the progression of diseases. The design of oral antioxidant nanoenzymes for scavenging ROS has emerged as a promising strategy to intervene in IBD. However, the practical application of these nanoenzymes is limited due to their single catalytical property and significantly impacted by substantial leakage in the upper gastrointestinal tract. This study introduces a novel oral delivery system, SP@CS-SeNPs, combining natural microalgae Spirulina platensis (SP), which possesses superoxide dismutase (SOD)-like activity, with chitosan-functionalized selenium nanoparticles (CS-SeNPs) that exhibit catalase-like activity. The SP@CS-SeNPs system leverages the dual catalytic capabilities of these components to initiate a cascade reaction that first converts superoxide anion radicals (O2•–) into hydrogen peroxide (H2O2), and then catalyzes the decomposition of H2O2 into water and oxygen. This system not only utilizes the resistance of the microalgae carrier to gastric acid and its efficient capture by intestinal villi, thereby enhancing intestinal distribution and retention but also demonstrates significant anti-inflammatory effects and effective repair of the damaged intestinal barrier in a colitis mice model. These results demonstrate that this oral delivery system successfully combines the features of microalgae and nanozymes, exhibits excellent biocompatibility, and offers a novel approach for antioxidant nanozyme intervention in IBD.

Oral ulcers are common in the oral mucosa. Frequent occurrences of oral ulcers commonly afflict patients, seriously impacting their daily life. Treatments with good anti-inflammatory and antibacterial properties are important for promoting the healing of oral ulcers. In this study, a multifunctional, soluble hyaluronic acid (HA) microneedle (MN) patch was prepared to promote oral ulcer healing. The tip layer of the MN patch was loaded with triamcinolone acetonide (TA) and epidermal growth factor (EGF) to inhibit inflammation and promote angiogenesis. Zeolitic imidazolate framework-8 (ZIF-8) was loaded onto the base layer of the MN patch, which effectively released Zn 2+ to mediate antibacterial effects. In addition, HA exerts a protective effect on the mucous membrane. Owing to these properties, the multifunctional MN patches were found to have good anti-inflammatory, antibacterial, and tissue-healing abilities, indicating that the multifunctional MN patch design successfully promoted the healing of oral ulcers.

Oral ulcers have periodicity and recurrence, and the etiology and causative mechanisms remain unclear; therefore, it is difficult to treat oral ulcers effectively. Current clinical treatment methods mainly include pain relief and administration of anti-inflammatories to prevent secondary infections and a prolonged recurrence cycle. However, these traditional treatment methods are administered independently and are susceptible to muscle movements and constant salivary secretion in the mouth, resulting in ineffective drug functioning. Therefore, development of a novel treatment to reduce wound infection and accelerate wound healing for oral ulcers is required for effective treatment. Herein, we report a multifunctional polysaccharide composite microneedle patch based on hyaluronic acid (HA) and hydroxypropyl trimethyl ammonium chloride chitosan (HACC) loaded with dexamethasone (DXMS) and basic fibroblast growth factor (bFGF) for oral ulcer healing. DXMS and bFGF encapsulated the HA tip portion of the microneedle patch, endowing the microneedle patches with anti-inflammatory and angiogenic properties. HACC was applied to the back of the microneedle patch, adding antibacterial properties. The experimental results indicated that the prepared dressings exhibited good antibacterial activity and effectively promoted cell migration growth and angiogenesis. More importantly, animal experiments have shown that multifunctional microneedle patches can effectively promote oral ulcer healing. Thus, these novel multifunctional polysaccharide composite microneedle patches have great potential for oral ulcers treatment.

Oral ulceration is the most common oral mucosal disease. Oral mucosal ulcers are extremely painful, may interfere with eating and speaking, and potentially complicate systemic symptoms in severe cases. The humid and highly dynamic environment of the oral cavity makes local drug administration for treating oral mucosal ulcers challenging. To overcome these challenges, we designed and prepared a novel dissolving microneedle (MN) patch containing multiple drugs in a core-shell to promote oral ulcer healing. The MNs contained a methacrylate gelatin shell layer of basic fibroblast growth factor (bFGF), a hyaluronic acid (HA) core loaded with dexamethasone (DXMS), and zeolite imidazoline framework-8 (ZIF-8) encapsulated in the HA-based backplane. Progressive degradation of gelatin methacryloyl (GelMA) from the tip of the MN patch in the oral mucosa resulted in sustained bFGF release at the lesion site, significantly promoting cell migration, proliferation, and angiogenesis. Moreover, the rapid release of HA and, subsequently, DXMS inhibited inflammation, and the remaining MN backing after the tip dissolved behaved as a dressing, releasing ZIF-8 for its antimicrobial effects. This novel, multifunctional, transmucosal core-shell MN patch exhibited excellent anti-inflammatory, antimicrobial, and pro-healing effects in vivo and in vitro , suggesting that it can promote oral ulcer healing.

Macrophage M2 polarization plays a pivotal role in breast cancer development. The present study aimed to investigate the interplay of the Leupaxin (LPXN)/HDAC6/EGR2 axis in breast cancer and its impact on macrophage M2 polarization. Our findings indicate that LPXN overexpression in breast cancer tissues correlates with M2 macrophage polarization. To investigate LPXN's potential role, we conducted siRNA-mediated silencing in macrophages. In a breast cancer cell-macrophage co-culture system, LPXN silencing was associated with reduced cancer cell proliferation, decreased M2 polarization markers, and diminished HDAC6 expression. BIOGRD and experimental data suggest a regulatory relationship between LPXN and HDAC6. Notably, HDAC6 inhibition partially reversed the pro-M2 effects of LPXN overexpression. Further mechanistic studies revealed that HDAC6 interacts with EGR2, functioning as its deacetylase and negatively regulating EGR2 expression. EGR2 silencing partially attenuated the anti-M2 effects observed with LPXN knockdown. In murine breast cancer models, LPXN silencing was linked to increased M1 macrophage markers and reduced tumor burden. These findings suggest LPXN may influence breast cancer progression through HDAC6/EGR2-mediated regulation of macrophage polarization. In conclusion, our study demonstrated that the LPXN/HDAC6/EGR2 axis promotes breast cancer progression by augmenting macrophage M2 polarization. Graphical

To improve the osseointegration of Ti-6Al-4V implants, a Zn-, Mg-, and Cu-doped composite coating was fabricated via soft sparking micro-arc oxidation (S-MAO). The resulting S-MAO coating retained a porous microstructure and was successfully doped with the intended elements (Zn, Mg, Cu). The Zn/Mg/Cu components in the composite coating potentiated macrophage polarization towards the reparative M2 phenotype, as evidenced by an approximately 1.4-fold upregulation of CD206⁺ and a 31 % downregulation of CD86⁺. This immunomodulatory effect subsequently upregulated the expression of osteogenic genes BMP2, COL1A1, Runx2, and OCN by approximately 2.2-, 2.1-, 2.6-, and 1.7-fold, respectively. Furthermore, MC3T3-E1 cells cultured on the composite coating exhibited a characteristic spread morphology with significantly increased pseudopodia number and length, indicating enhanced cell adhesion and early osteogenic commitment. Additionally, the coating significantly enhanced ALP activity and mineralized nodule formation, which are associated with the direct osteogenic effects of Zn, Mg, and Cu. In summary, the composite coating promotes osteoblast differentiation and mineralization by modulating the immunomodulatory microenvironment and directly inducing the release of osteogenic factors. Therefore, this multi-element co-doping strategy offers a promising approach for developing bioactive titanium implants with enhanced osseointegration.

This study investigated the effect of dielectric barrier discharge (DBD) on sea cucumber polysaccharide (SP-2) and evaluated its anti-inflammatory properties. The SP-2 was depolymerized by applying an input voltage of 60~90 V for 3~9 min. The features of the products were examined using high-performance gel permeation chromatography, HPLC-PAD-MS, and the Fourier transform infrared (FTIR) spectrum. The anti-inflammatory properties of the product were investigated by measuring nitric oxide (NO) release, ROS accumulation, and cell migration using RAW264.7 cells (LPS-induced or not-induced). The results showed SP-2 depolymerized into homogeneous and controllable-size oligosaccharide products. The depolymerized ratio can reach 80%. The results of the measurement of reducing sugars indicate that SP-2 was cleaved from within the sugar chain. The SP-2 was deduced to have a monosaccharide sequence of GlcN-Man-Man-Man-Man-Man based on the digested fragment information. The depolymerization product restrained the release of NO and the accumulation of ROS. By testing the RAW264.7 cell scratch assay, it was found that it enhances the migration of immune cells. DBD degradation of SP-2 leads to homogeneous and controllable-size oligosaccharide products, and this technique can be used for polysaccharide structure analysis. The depolymerized product of SP-2 has an anti-inflammatory capability in vitro.Keywords:dielectric barrier discharge;polysaccharide;degradation;RAW264.7 cell;migration

Selenium nanoparticles (Se NPs) have received increasing attention as a new alternative source to other forms of selenium in nutritional dietary supplements; however, the limited stability and pronounced tendency of selenium nanoparticles (Se NPs) to aggregate in aqueous environments have significantly constrained their practical applications. In this study,Poria cocospolysaccharide-modified Se NPs (PCP-Se NPs) were synthesized by the selenite/ascorbic acid chemical reduction method. PCP-Se NPs exhibited a uniformly dispersed spherical morphology with an average particle size of 66.64 ± 0.30 nm, and displayed an amorphous crystal structure. Compared to unmodified Se NPs, the PCP-Se NPs exhibited low Se release (8.83 ± 0.73%) after simulated gastrointestinal digestion, and they had excellent storage stability and salt ion stability. PCP-Se NPs exhibited potent antioxidant activity manifested by the effective scavenging of DDPH and ABTS radicals. PCP-Se NPs were efficiently internalized by RAW264.7 cells and released into the cytoplasm by a lysosomal escape mechanism, thereby effectively reducing intracellular inflammatory factor levels (the levels of MPO, NO, iNOS, TNF-α, IL-1β, and IL-10 in the PCP-Se NPs treatment group were 0.38 ± 0.013-fold, 0.26 ± 0.02-fold, 0.36 ± 0.02-fold, 0.57 ± 0.03-fold, 0.35 ± 0.02-fold, and 2.07 ± 0.16-fold that of the LPS group, respectively), alleviating oxidative stress (the levels of CAT, SOD, GSH, and MDA in the PCP-Se NP-treated group were 2.48 ± 0.02-fold, 1.91 ± 0.11-fold, 3.16 ± 0.28-fold, and 0.46 ± 0.03-fold that of the LPS group, respectively), and maintaining mitochondrial membrane potential stability. This study provides a basis and reference for improving the stability of Se NPs and developing novel selenium-enriched dietary supplements.