CD86 Recombinant Rabbit Monoclonal Antibody

Preventing post-surgical recurrence and metastasis in advanced gastric cancer through tumor vaccines necessitates a more surgically compatible strategy. Here, we propose an intraoperatively applicable platform featuring a self-adjuvant tumor vaccine co-delivered with PD-1 blockade in fibrin gel (FG) to inhibit post-surgical tumor relapse. First, the tumor cell membrane vaccine is modified via simple insertion of DSPE-PEG-αCD40, which simultaneously endows the vaccine with targeting and self-adjuvant effects on antigen-presenting cells (APCs). This αCD40-modified vaccine (Vax-αCD40) significantly stimulates dendritic cell maturation and reprograms macrophages toward pro-inflammatory phenotypes in vitro and in vivo. Moreover, when Vax-αCD40 and αPD-1 are encapsulated within FG to form an adhesive “vaccine pool”, a positive feedback loop of CD40 expression-αCD40 stimulation on APCs exerts synergistic immune activation at the surgical site. In mouse models, this co-delivery system effectively suppresses local recurrence and peritoneal metastasis, which is associated with increased APC infiltration, cytotoxic CD8 + T cell expansion, and durable immune memory. This strategy represents a translatable approach for preventing recurrence in gastrointestinal malignancies.

Glaucoma is a leading cause of irreversible blindness, characterized by the progressive degeneration of retinal ganglion cells (RGCs) and optic nerve damage. Although current intraocular pressure (IOP)-lowering therapies exhibit varying degrees of efficacy in preventing RGC loss, neurodegeneration can persist even in cases where IOP remains within the normal range, underscoring the need for direct neuroprotective strategies. Emerging evidence suggests that neuroinflammation mediated by retinal microglia plays a pivotal role in the pathogenesis of glaucoma. Here, a nucleic acid-based nanotherapeutic platform is proposed that employs tetrahedral framework nucleic acids (tFNAs) conjugated with microRNA-124 (miR-124), referred to as Tmi, to achieve targeted immunomodulation. Compared with conventional delivery systems, this self-assembled nanostructure exhibits superior cellular penetration and nucleic acid protection capabilities. Mechanistic studies demonstrate that Tmi-mediated inhibition of the STAT3 pathway attenuates excessive microglial activation, reduces migration-associated inflammation, and suppresses pathological cell migration in an acute ocular hypertension model. This is an alternative treatment strategy beyond intraocular pressure control, offering greater possibilities for exploring therapies for acute high intraocular pressure glaucoma.

Background Lung cancer exhibits high mortality and incidence rates, with tumor-associated macrophages (TAMs) serving as critical contributors to cancer progression. This study investigates the unexplored mechanistic role of HRD1—an E3 ubiquitin ligase implicated in cancer — in orchestrating TAM polarization to affect lung cancer pathogenesis. Methods HRD1 expression in lung cancer using TCGA database and validated its impact via IHC. THP-1 cells and macrophages isolated from murine tumor tissues via magnetic bead sorting were transfected with the oe-HRD1 plasmid, followed by flow cytometry, ELISA, and RT-qPCR assays to investigate HRD1's regulatory effects on macrophage polarization and function. Co-IP was employed to investigate interactions between USP7 and HRD1/PD-L1, while Immunofluorescence elucidated underlying mechanisms. Results HRD1 was highly expressed in lung cancer and promotes tumor growth in tumor-bearing mice and proliferation in THP-1 cells. Strikingly, both in vivo and in vitro overexpression of HRD1 drove macrophage M2 polarization. Mechanistically, USP7 interacted independently with HRD1 and PD-L1, while HRD1 binding to USP7 facilitated PD-L1 ubiquitination. Furthermore, HRD1 overexpression upregulated USP7 expression, thereby enhancing M2 polarization. Conclusion HRD1 promotes lung cancer progression by regulating TAM M2 polarization via USP7, offering novel therapeutic targets and diagnostic perspectives for early-stage lung cancer intervention.

This study aims to investigate the effect of exosomes derived from olfactory mucosa mesenchymal stem cells (OM-MSCs-Exo) on microglial polarization and its potential therapeutic role in Alzheimer’s disease (AD). OM-MSCs-Exo were isolated and purified from the mice olfactory mucosa, followed by phenotypic characterization. Proteins transferred by OM-MSCs-Exo were screened using proteomic analysis. The AD model was established in microglial cells and mice with Aβ 1–42 . Immunofluorescence and biochemical assays were employed to assess the impact of OM-MSCs-Exo and its secreted protein FGFR1 on microglial polarization. Protein–protein interactions and immunoprecipitation were used to identify the target proteins of FGFR1 in microglial cells. Additionally, the effects of OM-MSCs-Exo-induced microglial polarization on neuronal inflammation and cognitive function in mice were evaluated. OM-MSCs-Exo were successfully isolated and purified. FGFR1 was significantly upregulated in OM-MSCs-Exo compared to OM-MSCs. Aβ 1–42 induced M1 polarization and suppressed M2 polarization of microglia, which was reversed by OM-MSCs-Exo. FGFR1 overexpression in OM-MSCs-Exo further enhanced M2 polarization in microglial cells. Phospholipase C gamma 1 (PLCγ1) was identified as the target of FGFR1, and knocking down PLCγ1 reversed the effects of FGFR1-overexpressing OM-MSCs-Exo. OM-MSCs-Exo alleviated cognitive decline and neuroinflammation in AD mice, with FGFR1 overexpression further enhancing these effects. OM-MSCs-Exo promote M2 polarization of microglia in AD mice through the FGFR1/PLCγ1 pathway, alleviating neuronal inflammation and cognitive dysfunction.

Cancer-induced bone pain (CIBP), a debilitating complication of metastatic bone cancer, necessitates prompt and effective therapeutic interventions. Sinomenine (SIN), an alkaloid extracted from Sinomenium acutum , demonstrates anti-inflammatory and analgesic properties; nevertheless, its efficacy and mechanisms in CIBP management is inadequately investigated. This study looked at how SIN affected CIBP in a female rat model with bone discomfort caused by tumor implantation and BV2 microglial cells that were activated by lipopolysaccharide (LPS). Behavioral assessments (von Frey filaments, spontaneous activity scoring) showed that SIN administration significantly alleviated mechanical allodynia and ambulatory deficits in CIBP rats. Immunofluorescence assay revealed SIN-mediated suppression of pro-inflammatory microglial polarization (reduced IBA1+/CD86+ cells) and promotion of anti-inflammatory phenotypes (increased IBA1+/CD206+ cells), paralleled by decreased pro-inflammatory mediators and elevated anti-inflammatory mediators. Mechanistic investigations identified NF-κB p65 activation in both CIBP rats and LPS-treated BV2 cells. SIN induced p65 ubiquitination and proteasomal degradation, as evidenced by cycloheximide/MG132 assays, thereby attenuating NF-κB signaling. Notably, p65 overexpression in CIBP rats reversed SIN’s analgesic effects and restored pro-inflammatory microglial activation, confirming p65’s key role in SIN-mediated modulation. These findings collectively demonstrate that SIN alleviates CIBP by partially suppressing NF-κB p65 activity via ubiquitination-dependent degradation, which subsequently inhibits neuroinflammatory microglial polarization. This study positions SIN as a promising candidate for managing cancer-related bone pain.

Background: Postoperative cognitive dysfunction (POCD) is a common and serious complication in older adult patients. While the tyrosine kinase ABL1 has been implicated in neurodegenerative diseases, its specific role in POCD remains unexplored. This study aims to investigate whether ABL1 influences POCD in aged mice by regulating microglial autophagy and neuroinflammation via the mTOR/ULK1 pathway. Methods: An aged mouse model of POCD was established, and ABL1 silencing and 3-Methyladenine (3-MA) were used to intervene in mice. The Novel Object Recognition Test (NORT) assessment and water maze experiment were conducted. qRT-PCR quantified the mRNA levels of inflammatory cytokines, hippocampal damage was assessed by immunofluorescence, and western blot analyzed the protein expression of autophagy-related genes and the mTOR/ULK1 pathway. Co-Immunoprecipitation (CO-IP) was used to detect the binding of ABL1 to mTOR. In vitro experiments used microglial cells, where ABL1 silencing and rapamycin (Rapa) were used to construct a cellular model and conduct relevant cell experiments. Results: ABL1 silencing or 3-MA rescued cognitive deficits in aged POCD mice, concurrently mitigating neuroinflammation, microglial activation, and aberrant autophagy in the hippocampus. We established ABL1 as a direct binding partner of mTOR. Silencing ABL1 activated the mTOR pathway, leading to ULK1 inhibition and suppression of autophagic activity. Consistent with these in vivo results, ABL1 knockdown in microglia attenuated pro-inflammatory responses, inhibited autophagy, and conferred protection against neuronal damage. Conclusions: ABL1 exacerbates POCD in aged mice by promoting microglial autophagy and neuroinflammation through the mTOR/ULK1 signaling pathway. Targeted inhibition of ABL1 may represent a novel therapeutic strategy for preventing or treating POCD.