西安医学院

The inflammatory response in the cerebral cortex serves an important role in the progression of secondary injury following traumatic brain injury (TBI). The NLR family pyrin domain containing 3 (NLRP3) inflammasome is necessary for initiating inflammation and is involved in various central nervous system disorders. The aim of the present study was to investigate the neuroprotective effect of resveratrol and elucidate the underlying mechanisms of resveratrol associated regulation of the NLRP3 inflammasome in TBI. The results demonstrated that the activation of NLRP3, caspase‑1 and sirtuin 1 (SIRT1), enhanced the production of inflammatory cytokines and reactive oxygen species (ROS) following TBI. Administration of resveratrol alleviated the degree of TBI, as evidenced by the reduced neuron‑specific enolase (NSE) and brain water content (WBC). Resveratrol pretreatment also inhibited the activation of NLRP3 and caspase‑1, and reduced the production of inflammatory cytokines and ROS. In addition, resveratrol further promoted SIRT1 activation. Furthermore, the suppressing effect of resveratrol on the NLRP3 inflammasome and ROS was blocked by the SIRT1 inhibitor, sirtinol. The results revealed that the activation of the NLRP3 inflammasome and the subsequent inflammatory responses in the cerebral cortex were involved in the process of TBI. Resveratrol may attenuate the inflammatory response and relieve TBI by reducing ROS production and inhibiting NLRP3 activation. The effect of resveratrol on NLRP3 inflammasome and ROS may also be SIRT1 dependent.

Developing polyphenol-loaded hydrogels can not only address the poor antibacterial and anti-inflammatory performance of single hydrogels, but also overcome the disadvantages of low bioavailability and poor stability of bioactive polyphenols. A novel cyclodextrin supramolecular drug-loaded hydrogel was constructed in this study, using carboxymethyl-β-cyclodextrin and polyethylene glycol-functionalized chitosan as raw materials, β-glycerophosphate sodium as the crosslinking agent and tannic acid (TA) as the drug model. The construction was realized through the synergistic effects of chemical crosslinking, electrostatic interaction, host-guest interaction, hydrogen bonding interaction, as well as supramolecular assembly driven by multiple interaction. Influence of various factors on the gelation time was investigated, and the properties of swelling, adsorption, rheology, antioxidant, drug-controlled release, antibacterial, and biocompatibility were systematically evaluated. Under optimal conditions, the gelation time of the cyclodextrin supramolecular hydrogel was 18 s, and the adsorption capacity for TA reached 315.2 mg/g, achieving controlled, sustained and long-lasting release. When the concentration of the drug-loaded gel reached 25 µg/mL, the DPPH radical scavenging rate was 91.9

Optimizing the immune microenvironment is essential for successful implant osseointegration. In this study, four different nano/microstructures were fabricated on polyetheretherketone (PEEK) substrates by varying the agitation speed during sulfonation to influence osteoimmunomodulation and implant integration. The results indicate that nano/microstructures with minimal dimensions (SP450) inhibit actin polymerization by reducing calcium influx through PIEZO1, activating the anti-inflammatory M2 macrophage phenotype. Among the tested specimens, SP450 exhibited the lowest expression levels of tumor necrosis factor-α and interleukin-1β while releasing the highest levels of anti-inflammatory factors, including interleukin-4 and interleukin-10. This optimized immune environment promotes the osteogenesis of MC3T3-E1 pre-osteoblasts and enhances the osseointegration of PEEK implants. Transcriptomic analysis and validation experiment further revealed that SP450 inhibits osteoclastic differentiation by down-regulating transforming growth factor-β2 and suppressing the NF-κB signaling pathway. These findings suggest that manipulating the surface topography of PEEK implants is an effective strategy for enhancing osseointegration with promising clinical applications.

Diabetic wounds usually involve disorganized redox and immune homeostasis and are prone to bacterial infection, often leading to delayed healing and worse outcomes. However, existing therapeutic strategies cannot simultaneously achieve potent antibacterial action and temporal microenvironment modulation. Herein, a self-evolving hyaluronan/poly(aspartic acid) hydrogel dressing integrating in situ Ag+-to-Ag nanozyme conversion function and hydrolyzable Fe3N/Fe3O4 nanoheterojunction (nHJ) is presented to meet the intricate requirements of consecutive healing stages. At infectious inflammatory stage, nHJ-based self-oxygenated photodynamic and photothermal effects synergize with Ag+ to combat multidrug-resistant biofilm-forming bacteria. Subsequently, Ag nanozymes with superoxide dismutase/catalase-like activities continuously scavenge reactive oxygen species while generating oxygen, facilitating macrophage M1-to-M2 repolarization and ensuing inflammatory-to-proliferative phase transition. Accumulated ammonia enhances cell proliferation, migration and angiogenesis. The dressing demonstrates exceptional biocompatibility and bioactivity in accelerating Staphylococcus aureus-infected full-thickness cutaneous wound healing in a diabetic rat model, as validated by hemostatic, broad-spectrum antibacterial, antioxidative and immunomodulatory abilities, enhanced oxygenation and cell proliferation, and extensive collagen deposition, vascularization and re-epithelialization. RNA-seq results further reveal the activation of multiple pro-healing signaling axes. Consequently, this platform offers a powerful dynamic strategy of realizing robust antibacterial activity and active temporal niche modulation to guide the healing of infected diabetic wounds.

Resveratrol is a natural polyphenol found in plants that has attracted significant research attention for its antitumor potential. With the continuing research on the tumor microenvironment and metabolic reprogramming, the roles of resveratrol in tumor cell metabolism and immune cell function have gained increasing attention. Recent studies have shown that resveratrol disrupts tumor cell metabolism and prevents tumor cell growth and metastasis by inhibiting metabolic processes such as glycolysis and fatty acid production. Furthermore, resveratrol regulates immune cells such as T cells, macrophages, and natural killer cells and enhances antitumor immune responses. In this article, we report the recent research progress on the use of resveratrol for tumor therapy. Specifically, we focus on its regulatory effect on tumor metabolism and the immune microenvironment and discuss its potential in combination with a new therapeutic strategy.