SUMOylation plays critical roles in both initiation and development of atherosclerosis. SUMO-specific protease 3 (SENP3), a SUMO-specific protease that targets SUMO2/3 for deSUMOylation, is involved in vascular remodeling and the modulation of macrophage functions. Here, we probed for the role of SENP3 in macrophages in the development of atherosclerosis. Stable and unstable plaques were collected from patients with atherosclerosis. A macrophage-specific SENP3 knockout mouse (Senp3Mac-KO) was generated and performed for a murine atherosclerosis model. Transcriptional sequencing was performed to identify potential mechanisms. SENP3 expression in macrophages was increased in unstable plaques, compared to stable plaques. The mean fluorescence intensity of SENP3 in macrophages infiltrating carotid plaques was positively correlated with circulating pro-inflammatory cytokines, low density lipoprotein (LDL-C), and triglycerides in atherosclerosis patients. Senp3Mac-KO mice exhibited a markedly reduced atherosclerotic plaque area in the aorta, compared to wild-type mice. Knockdown of SENP3 in macrophages resulted in decreased secretion of pro-inflammatory cytokines, increased secretion of anti-inflammatory factors, and reduced foam cell formation. Transcriptional analysis identified significant enrichment in Toll-like receptor (TLR4) signaling pathway modulated by SENP3. Genetic deletion of either TLR4 (Tlr4-/-) or Sterol O-Acyltransferase 2 (SOAT2) (Soat2-/-) attenuated the exacerbation of atherosclerosis development induced by SENP3 overexpression. Furthermore, SENP3 regulated TLR4 and SOAT2 expression indirectly via the transcription factor MYC rather than through direct deSUMOylation of TLR4 or SOAT2 themselves. Downregulation of SENP3 in macrophages suppresses pro-inflammatory cytokine release by inhibiting TLR4 signaling and reduces foam cell formation by impeding SOAT2 expression, both mediated by the transcription factor MYC, thereby attenuating the development of atherosclerosis. Hence, SENP3 may represent a potential therapeutic target in atherosclerosis.

Neutrophils play a dual role in inflammatory bowel diseases (IBD), contributing to both host defense and tissue damage. Among them, CXCR4+CD62Llo aged neutrophils have been implicated in chronic inflammation, though their precise involvement in the pathogenesis of IBD remains unclear. This study aimed to explore the functional characteristics and therapeutic potential of aged neutrophils in IBD. Samples of peripheral blood and colonic biopsies from 61 patients with IBD (47 with active disease, 14 with inactive disease) and 36 healthy controls were analyzed to quantify aged neutrophils. Flow cytometry, immunofluorescence, and neutrophil-peripheral blood mononuclear cell co-culture assays were used to assess their function. The therapeutic effects of the CXCR4 antagonist AMD3100 were tested in a dextran sulfate sodium-induced acute colitis model. Our results demonstrated a marked accumulation of aged neutrophils in both peripheral blood and inflamed intestinal tissues of patients with active IBD, and their abundance was positively correlated with disease severity. Functionally, these cells displayed elevated β-galactosidase activity, heightened reactive oxygen species generation, enhanced formation of neutrophil extracellular traps, and increased secretion of pro-inflammatory cytokines, including IL-6, IL-17A, and TNF-α. Additionally, aged neutrophils were associated with enhanced T- and B-cell activation. CXCR4 inhibition reduced aged neutrophil accumulation, alleviated inflammation, and restored intestinal barrier integrity by upregulating tight junction proteins (ZO-1, occludin). Collectively, these findings indicate that aged neutrophils may contribute to the pathogenesis of IBD by linking innate and adaptive immunity, amplifying inflammatory cascades, and promoting mucosal injury. Targeting these cells represents a promising therapeutic strategy for IBD.

Mycobacterial fusion protein REA eliciting anti-tumor activity through activation of innate immunity.

Mechanism of recombinant Trichinella spiralis antigen p53 alleviating experimental colitis via the IDO-AhR Axis.

NKG2D-based CAR-T cells for synovial sarcoma: A preclinical proof-of-concept study.

Standardized Centella asiatica extract (ECa 233) mitigates chlorhexidine-induced cytotoxicity and promotes oral wound repair via immunomodulation and angiogenesis.

Cytokine-based NK cell engineering for cancer immunotherapy.

Myopia is a complex refractive disorder and a leading cause of visual impairment worldwide. Inflammation plays a crucial role in the onset and progression of myopia. This study aimed to investigate the role of atropine in modulating inflammation-induced alterations in dopamine and its receptors in primary human scleral cells under in vitro experimental conditions. Human primary scleral cells were exposed to long-term inflammatory conditions in the presence or absence of atropine or dopamine hydrochloride. Following treatment, gene and protein expressions were analyzed for inflammatory markers, dopamine receptors, and extracellular matrix (ECM) using quantitative polymerase chain reaction, immunoblotting, and immunofluorescence. Secretory cytokines and dopamine levels were measured using an automated enzyme-linked immunosorbent assay system. In primary human scleral cells, atropine treatment increases the dopamine receptor expression. Prolonged inflammatory stimulation led to a marked reduction in dopamine and its receptor (D1-D2) expression, which was effectively restored following atropine treatment in scleral cells. Under inflammatory conditions, atropine significantly suppressed pro-inflammatory cytokines expression at both the transcript and protein levels and mitigated the inflammation-induced dysregulation of ECM genes. Our findings demonstrate atropine restores inflammation-induced dopaminergic and extracellular matrix dysregulation in human scleral cells, highlighting its dual anti-inflammatory and neuro-modulatory roles. The restoration of dopamine signaling and ECM balance underscores atropine's potential as a therapeutic agent for myopia.

Astrocytes, the most abundant glia subtype, exert a wide range of functions, many of which are essential for maintaining neuronal homeostasis. A variety of neurotransmitter receptors are expressed on astrocytes allowing them to sense extracellular signals and respond by releasing neuroactive mediators. Among them, a wide variety of G protein-coupled receptors have been detected, including those for dopamine (DA), known to play a major role in modulating astrocytic activity. Evidence that astrocytic DA D2 receptors (D2R) increase the release of trophic factors and suppress neuroinflammation has been provided. Thus, DA signaling in astrocytes may be crucially involved in the mechanisms underlying the degeneration of DA neurons in Parkinson's disease (PD). In this study, human astrocytes were generated from induced pluripotent stem cell (iPSC) lines derived from two PD patients bearing G2019S LRRK2 kinase activating mutation. The effect of the PD-related mutation in astrocytes was analyzed, focusing on DA receptor's expression and localization. As expected, astrocytes carrying G2019S mutation in LRRK2 displayed a reactive phenotype with increased secretion of inflammatory cytokines and reduced ability to support DA neurons' trophism in astrocytes/neurons co-culture experiments. Intriguingly, PD astrocytes exhibited reduced membrane expression of D2R. Inhibiting the abnormally increased kinase activity was able to revert the PD astrocytes' reactive phenotype and to rescue the D2R membrane localization. We thus provide new insights into how G2019S mutation in LRRK2, by disrupting the astrocytic physiological localization of D2R, may impair protective DA signaling, resulting in increased neuroinflammation and neuronal damage.

Tiger nut (Cyperus esculentus L.) meal peptides (TMP) are bioactive peptides prepared by hydrolyzing tiger nut meal-a by-product of tiger nut oil extraction-with alkaline protease. These peptides have demonstrated promising immunomodulatory potential. In this study, proteins were extracted from tiger nut meal using the alkali dissolution and acid precipitation method. The enzymatic hydrolysis conditions were then optimized through single-factor experiments and response surface methodology. The optimal hydrolysis conditions were determined as follows: hydrolysis time 4h, pH 10, enzyme dosage 9000 U/g, and temperature 46°C. Under these conditions, the degree of hydrolysis reached (24.87 ± 0.91%). Subsequently, a peptide fraction with a molecular weight of <3kDa was obtained via ultrafiltration. In vitro, this fraction significantly promoted the proliferation of mouse splenic lymphocytes and induced the secretion of pro-inflammatory cytokines, including interleukin-2 (IL-2), interferon-γ (IFN-γ), and tumor necrosis factor-α (TNF-α). In vivo experiments showed that TMP effectively improved immune function in cyclophosphamide (CTX)-induced immunosuppressed mice, as indicated by increased immune organ indices, elevated serum levels of both pro-inflammatory cytokines (IL-2, IFN-γ, and TNF-α) and the anti-inflammatory cytokine interleukin-4 (IL-4), and alleviated histopathological damage in spleen tissue. This study provides theoretical support for the development of TMP in immunomodulatory products and expands the potential application of tiger nut by-products in the functional food industry.

Albumin-bound alkylated resiquimod for enhanced cancer immunotherapy.

Huangqin Qingre Chubi Capsule modulates the lncRNA AP005432.1/PI3K/AKT axis and is associated with improved self-perception of patients and inflammation in ankylosing spondylitis.

Inflammation participates in the development and progression of chronic diseases such as diabetes, cancer, and neurodegenerative disorders. Therefore, the search for novel anti-inflammatory agents is always required. Herein, we report a series of methoxylated 3,4-diarylpyrazoles with potent anti-inflammatory activity in the 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced topical edema. Most derivatives reduced phorbol's toxicity by more than 50%. The anti-inflammatory activity of the trimethoxylated analog 3r reached 90% inhibition and surpassed that of celecoxib. 3r also reduced the secretion of myeloperoxidase (MPO) and pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6). Micrographs of the ear's tissue clearly showed a decrease in thickness and infiltration of neutrophils, which correlates with the reduction of MPO and cytokines. Finally, molecular docking suggested that the series could inhibit cyclooxygenases and displayed a binding mode like that of celecoxib, though the enzymatic assay will be performed in future work.

Characterization of a polysaccharide from Rhodobryum giganteum and its activation effects on TLR4/PI3K-Akt/IκBα pathway.

Liver transplantation (LT) is the definitive treatment for end-stage liver diseases such as hepatocellular carcinoma (HCC) or cirrhosis, in a clinical context increasingly influenced by the high prevalence of Metabolic Dysfunction-Associated Steatotic Liver Disease. Organ shortages have expanded the use of extended-criteria donor grafts, including steatotic livers from donors after brain death or cardiocirculatory death. However, graft steatosis remains a major risk factor for ischemia/reperfusion (I/R) injury, early allograft dysfunction, and posttransplant outcomes, and current protective strategies are insufficient to fully overcome these challenges. Visceral adipose tissue (VAT) is an active endocrine and immunometabolic organ that can shape systemic inflammation and immune tone. Clinical studies report an association between increased VAT and I/R injury, graft dysfunction, rejection, frailty, and HCC recurrence after LT, particularly in recipients with obesity and in recipients transplanted for cirrhosis and/or HCC. Under stress conditions, dysfunctional VAT shifts toward a proinflammatory phenotype characterized by altered secretion of cytokines, adipokines, chemokines, and lipid mediators. This review analyzes the role of the adipose tissue-liver axis in LT, with emphasis on how adipose-related mediators may modulate I/R injury and alloimmune responses in clinically relevant settings. We synthesize evidence from human cohorts and preclinical LT and warm I/R models, highlight major knowledge gaps related to tissue-source attribution and context-dependent mechanisms, and discuss emerging therapeutic strategies to modulate adipose tissue inflammation and immunometabolic signaling. Integrating adipose biology into LT research may help refine risk stratification and identify new avenues to improve graft utilization and long-term outcomes.

Immunotherapy has revolutionized the treatment of cancers, infections, and autoimmune disorders by harnessing immune mechanisms such as signal recognition, intracellular cascades, and mediator release. However, clinical translation remains hindered by poor specificity, dysregulated signaling, and heterogeneous responses, leading to toxicity and resistance. Synthetic biology-engineering programmable cellular systems-provides transformative strategies to overcome these barriers. Through designed receptors, modular signaling circuits, and precision-controlled immune behaviors, it enables next-generation therapies with enhanced specificity and tunability. Key advances include synthetic immune circuits that permit context-dependent functions such as logic-gated activation and feedback-controlled cytokine secretion. These innovations open avenues for personalized treatments, bridging bioengineering with immunology to maximize efficacy and minimize off-target effects. This review highlights the translational potential of synthetic biology in advancing precision immunotherapy for oncology and immune disorders.

Topical ionic liquid-mediated GLUT1 gene editing ameliorates psoriasis and prevents recurrence.

A multifunctional bimetallic MOF nanozyme orchestrating ferroptosis-apoptosis synergy for enhanced gastric tumor immunotherapy.

Promoting keratinocyte psoriasiform changes and IL-17RE expression: Potential role of GLT1D1 in linear psoriasis.

Astrocytes, long considered supportive cells of the central nervous system (CNS), have critical roles in innate immunity. This Review explores immune signaling pathways in astrocytes, including pattern recognition through Toll-like receptors, nucleic acid sensors and inflammasomes. These pathways enable the detection of danger signals and initiate protective responses and endogenous innate immune functions. Downstream signaling pathways, including the interferon, NF-κB and STAT3 pathways, mediate astrocyte reactivity and drive cytokine secretion, antiviral responses, phagocytosis and many other immune functions. While these responses are crucial for CNS health, their dysregulation can contribute to chronic inflammation and neurodegeneration in conditions such as Alzheimer's disease, Parkinson's disease, multiple sclerosis and amyotrophic lateral sclerosis. Additionally, astrocytes exhibit regional heterogeneity in their immune behaviors, which may influence disease trajectories. We highlight unresolved questions regarding the immune functions of astrocytes, their interplay with professional immune cells and their dual protective and pathological roles.