新闻与研究亮点

研究亮点

• Cianidanol reduces epidermal hyperplasia and abnormal collagen deposition in AD.
• Cianidanol alleviates AD symptoms by suppressing pro-inflammatory M1 polarization.
• CETSA and docking validate JAK2 as a direct target of Cianidanol in regulating AD.

摘要

Cianidanol (Cian), also known as (+)-catechin, is a naturally occurring flavonoid found in medicinal plants including Camellia sinensis and Violae herba. Its role in inflammatory skin disease has not been well defined. Human single-cell RNA sequencing data showed an increased proportion of M1-like macrophages in atopic dermatitis (AD). We therefore evaluated Cian in a 2,4-dinitrochlorobenzene-induced AD-like dermatitis mouse model and in RAW264.7 and THP-1 macrophage models. Cian alleviated skin lesions, reduced epidermal thickening, suppressed pro-inflammatory cytokine production, and restored anti-inflammatory responses. It also reduced CD86 expression without promoting a marked M2-like phenotypic shift. Mechanistically, Cian decreased the phosphorylation of Janus kinase 2 (JAK2) and signal transducer and activator of transcription 1 (STAT1). Molecular docking, molecular dynamics simulation, and cellular thermal shift assay supported a potential interaction between Cian and JAK2 in cell lysates. These findings indicate that Cian attenuates experimental AD-like inflammation in association with reduced M1-like macrophage activation and JAK2/STAT1 signaling, while its safety and pharmacokinetic profile require further investigation.

研究亮点

• Immune checkpoints act as central regulators linking inflammation and immunity.
• Inflammatory signals dynamically modulate checkpoint expression and function.
• Checkpoint pathways show dual roles in acute and chronic inflammatory states.
• Dysregulation of immune checkpoints contributes to tumors and autoimmune diseases.
• Targeting checkpoint–inflammation networks offers new strategies for precision immunotherapy.

摘要

Immune checkpoints (ICs) are receptors that regulate immune responses through both activating and inhibitory mechanisms. Key pathways, including programmed death 1, cytotoxic T-lymphocyte antigen 4, T cell immunoreceptor with Ig and ITIM domains, T-cell immunoglobulin and mucin-domain containing-3, and lymphocyte-activation gene 3, mediate bidirectional interactions between checkpoint signaling and inflammatory networks. The inflammatory microenvironment modulates IC expression through cytokines, metabolites, and oxidative signals, while persistent checkpoint activation promotes immunosuppression. This feedback loop contributes to multiple disease contexts, including cancer, autoimmune disorders, infections, and metabolic inflammation. Immune checkpoint inhibitors not only enhance antitumor immunity but also reshape systemic immune networks, which is closely associated with immune-related adverse events. This review summarizes the molecular and cellular mechanisms by which ICs regulate inflammatory responses and highlights their roles across diverse pathological conditions. It further emphasizes the potential of targeting checkpoint–inflammation interactions to improve precision immunotherapy and therapeutic strategies for inflammatory diseases.

研究亮点

• SCFAs are critical immunometabolic signals linking gut microbiota to host inflammatory status.
• SCFAs act as molecular bridges to regulate inflammatory responses across multiple distant organs.
• Targeted SCFA-centered interventions hold promising translational potential.

摘要

The gut microbiota plays a fundamental role in maintaining host physiological homeostasis. Among the diverse metabolites produced by intestinal microbes, short-chain fatty acids (SCFAs) represent one of the most functionally significant groups. These metabolites arise primarily from the fermentation of non-digestible carbohydrates and serve as a major interface between microbial metabolism and host signaling. SCFAs possess anti-inflammatory properties in the intestinal microenvironment, promoting regulatory T cell differentiation and immune tolerance, and strategies aimed at increasing SCFA availability have been explored clinically. Traditionally viewed as local energy sources for colonocytes, SCFAs are now recognized as systemic signaling molecules capable of influencing distant organs. After absorption, they enter the portal circulation and reach peripheral tissues, where they modulate immune responses, metabolism, and tissue homeostasis. This review therefore mainly elaborates on the functions of SCFAs in various inter-organ axes as well as related therapeutic strategies.

研究亮点

• A. rectalis, linked to depleted secondary bile acids, was identified from IBD feces.
• A. rectalis alleviates DSS colitis by restoring microbiota and bile acid balance.
• Single-cell aloe gel coating (A. rectalis@Aloe) enhances gastric survival and gut colonization.
• A. rectalis@Aloe achieves superior colitis efficacy via microbiota–metabolite remodeling.

摘要

Gut microbiota dysbiosis and metabolic disturbances are implicated in inflammatory bowel disease (IBD). Current probiotic therapies are limited by poor bioavailability and inadequate colonic colonization. Here, we identified Agathobacter rectalis from IBD patient feces and demonstrated that it alleviated dextran sulfate sodium-induced colitis in mice by reshaping the gut microbiota and bile acid pool. To overcome these delivery barriers, we developed a single-cell encapsulation system using Aloe vera gel, a natural acid-resistant and anti-inflammatory hydrogel, and designated it as A. rectalis@Aloe to enhance probiotic bioavailability and targeted colonic retention. Comprehensive characterization confirmed that encapsulation significantly improved bacterial viability in simulated gastric fluid and enhanced colonic colonization. In murine colitis models, A. rectalis@Aloe synergistically suppressed inflammation, reinforced barrier function, modulated gut microbiota, and increased short-chain fatty acid production. Mechanistically, it inhibited cytokine–cytokine receptor interactions and the PI3K–Akt pathway. By synergistically enhancing gastric acid survival, mucosal colonization, and multi-pathway anti-inflammatory effects, this single-cell aloe gel encapsulation strategy offers a clinically promising and readily translatable platform for live biotherapeutics targeting the gut microbiota–metabolite axis in IBD.

研究亮点

• Vhb expression enhanced the Hly62 secretion efficiency by energy boosting.
• Hly62 exhibited little conformational interference and low immunogenicity.
• The bioactivities of therapeutic proteins can be detected with crude supernatant.
• The purified αTnb and αPnb-IL15 exhibited strong anti-inflammatory/tumor efficacy in vivo.

摘要

Escherichia coli currently serves as a widely used tool for therapeutic protein production; however, the high accumulation of heterologous proteins in the cytoplasm poses a risk of degradation by proteases and the formation of inactive inclusion bodies. Although it provides a direct secretion pathway, the application of the ATP-driven hemolysin A (HlyA) secretion system is severely hindered by its low efficiency. In this work, we first developed a novel Hly62 secretion system based on Vitreoscilla hemoglobin gene expression, which significantly improved the energy metabolism of the strain. The novel system facilitates the efficient secretion of different kinds of therapeutic proteins and enables rapid detection of bioactivities using crude supernatant. Moreover, the αTnb and αPnb-IL15 purified by one-step affinity chromatography exhibited not only potent anti-inflammatory and anti-tumor activities, but also low immunogenicity in vivo. High density cell fermentation and metabolomics analysis further validated the promotion effect of energy metabolism upregulation on the secretion efficiency of the HlyA secretion system. Therefore, our study established a rapid, simple, and efficient Hly62 secretion system based on energy metabolism engineering, revealing its significant application potential in biopharmaceutical manufacturing.

研究亮点

• Nanocarriers activate PRRs and the NLRP3 inflammasome, inducing IL-1β release and pyroptotic cell death.
• Nanocarrier-induced cellular stress reprograms immune metabolism toward a glycolytic phenotype.
• Reactive oxygen species and organelle damage regulate apoptosis, pyroptosis and ferroptosis pathways.
• Persistent nanoparticle accumulation impairs macrophage clearance, promoting chronic inflammation.
• Rational nanocarrier design strategies improve safety, biocompatibility and translational potential.

摘要

Nanocarriers have emerged as indispensable platforms for drug delivery, molecular imaging and precision diagnostics. Their rapidly expanding global application has intensified concerns regarding inflammation-driven toxicities and inter-individual variability in biological responses. Recent in vivo and translational clinical studies demonstrate that key physicochemical parameters of nanocarriers play decisive roles in protein corona formation, cellular uptake pathways, immune recognition and organ-specific biodistribution. Variations in these parameters significantly influence interactions with plasma proteins, macrophages and endothelial barriers, thereby modulating systemic exposure and clearance. Aberrant nanocarrier internalization has been associated with mitochondrial dysfunction, excessive reactive oxygen species generation, lysosomal destabilization and activation of pro-inflammatory signaling pathways, including nuclear factor kappa B and mitogen-activated protein kinase cascades. Collectively, these events may culminate in chronic inflammation, tissue injury or immunotoxicity, particularly in susceptible populations. A comprehensive understanding of nanocarrier–host interactions, combined with rational design strategies and population-specific risk assessment, is essential to maximize therapeutic efficacy while minimizing adverse inflammatory outcomes.