Inflammation Research最新文献

Background: In a ligature-induced periodontitis rat model, we tested oral citral (100 mg/kg, gavage) for 6 or 14 days and quantified alveolar bone loss, gingival cytokines, nitric oxide (NO), reactive oxygen species (ROS), MMP-2 activity, and plasma TNF-α.

Methods: Adult male rats received a ligature around the first lower right molar for 7 or 15 days to induce periodontitis, while control animals remained unligated. Alveolar bone loss was assessed by measuring the cementoenamel junction-bone crest distance. Gingival cytokines (TNF-α, IL-1β, IL-6, IL-10) and plasma TNF-α were determined by ELISA, gingival NO by chemiluminescence, MMP-2 activity by gelatin zymography, and local ROS by in situ detection.

Results: Citral did not affect healthy gingiva. In ligature-induced periodontitis, a 14-day citral treatment significantly reduced alveolar bone loss, downregulated pro-inflammatory cytokines, increased IL-10, decreased plasma TNF-α levels, and inhibited both NO production and MMP-2 activity. ROS accumulation in the gingival tissue was also attenuated.

Conclusion: These findings suggest that oral citral exhibits anti-inflammatory and antioxidant effects, thereby limiting alveolar bone loss in experimental periodontitis.

The study by Bai and Guo (Biol Direct 20(1):73. https://doi.org/10.1186/s13062-025-00669-0 , 2025) offers significant insights into the molecular mechanisms of LPS tolerance in macrophages. The authors identify a novel pathway wherein the transcription factor SPI1 (PU.1) directly upregulates the expression of the inhibitory receptor LILRB2, which in turn suppresses TLR8-mediated MyD88/NF-κB signaling to reinforce an immunosuppressive phenotype. While this work elegantly connects transcriptional regulation with functional immune modulation, several aspects warrant further discussion. The broad role of SPI1 necessitates confirming the specificity of its action on LILRB2 and excluding indirect effects on other tolerance regulators. The unconventional inhibition of TLR8, an endosomal viral RNA sensor, by LILRB2 raises questions about ligand specificity and context, particularly in scenarios of viral co-infection. Furthermore, the dominant role of TLR8 in LPS tolerance, a process canonically initiated by TLR4, merits additional validation to clarify its universality. Translational targeting of the SPI1/LILRB2 axis holds promise for reversing immune paralysis in sepsis or chronic inflammation, but potential risks demand careful evaluation using cell-specific approaches. Future work integrating epigenetic analyses, structural studies, single-cell transcriptomics from patients, and investigation of crosstalk with other immunoregulatory pathways will be crucial to fully establish the biological and clinical significance of these findings.

Background: Aquaporins (AQPs) are a class of channel proteins expressed on the cell membrane, responsible for facilitating the transport of water molecules and certain small solutes across the membrane. Their dysregulation is involved in the occurrence and progression of major lung diseases.

Findings: We systematically reviewed the expression and functional alterations of AQPs in acute lung injury (ALI), pneumonia, asthma, chronic obstructive pulmonary disease (COPD), pulmonary fibrosis (PF) and lung cancer, and integrated the potential molecular mechanisms. In addition, we examine the regulatory mechanisms of traditional Chinese medicine on lung AQPs, and summarizes the research progress of inhibitors and small molecular compounds that modulate AQPs in lung diseases.

Implications: AQPs may serve as promising therapeutic targets for lung diseases. This review offers novel insights and a foundation for the diagnosis, treatment, and drug development of lung diseases, positioning AQPs as a potential tool in combating these conditions.

Alzheimer's disease (AD) is the most prevalent neurodegenerative disease associated with accumulation of amyloid beta peptides and intracellular neurofibrillary tangles formed by hyperphosphorylated Tau. Autophagy, an evolutionarily conserved process of self-degradation and turnover of cellular constituents, is important for normal cell growth but may be defective in diseases. A growing body of data implies that autophagy strongly affects AD pathogenesis. Autophagy mediates degradation of damaged organelles and proteins as well as neurotoxic aggregates, by regulating their clearance. Thus, impaired autophagy may account for the accumulation of protein aggregates. Since AD is characterized by neuroinflammation, impaired mitochondrial and lysosomal functions, and the accumulation of protein aggregates, the roles of autophagy/mitophagy in Alzheimer's will be extensively evaluated. In the current review, we will discuss the connection between autophagy/mitophagy and Alzheimer's. It seems that Alzheimer-related proteins such as APOE4, TREM2, PSEN1/2, APP and Tau can regulate autophagy. In turn, depending on the cellular system and animal model, autophagy regulating proteins such as Atg7, BECN1, GSK3B, MAP1LC3B, SQSTM1, TFEB and VCP can affect AD progression as discussed. We will also describe the effect of sex and lifestyle impact on autophagy and AD. Finally, we will describe how the current knowledge may contribute to potential therapeutic strategies.

Objective and design: This study was designed to delineate how Piezo1 orchestrates macrophage polarization and autophagy in psoriasis and to determine whether the PI3K/AKT axis mediates these effects.

Material or subjects: Wild-type and Piezo1-knockout C57BL/6 mice were obtained from Vital River; human THP-1 monocytes and HaCaT keratinocytes were supplied by the Cell Bank of the Chinese Academy of Sciences.

Treatment: Imiquimod was applied topically for six consecutive days; Piezo1 was silenced with shRNA, and autophagy was pharmacologically inhibited (10 mM 3-MA) or activated (200 nM rapamycin).

Methods: HE staining, immunohistochemistry and RNA-seq were performed in vivo. Western blot, immunofluorescence and flow cytometry quantified LC3-II/I, p62, PI3K/AKT proteins and CD86/CD206; cytokines were measured by ELISA.

Results: Piezo1 expression was significantly elevated in psoriatic lesions (P < 0.01). Genetic deletion of Piezo1 markedly attenuated disease severity, accompanied by an increased LC3-II/I ratio, reduced p62 accumulation, and a pronounced decline in inflammatory cytokine levels. Macrophages shifted from M1 to M2, suppressing keratinocyte proliferation and promoting apoptosis. RNA-seq confirmed the PI3K/AKT pathway as the key mediator.

Conclusions: Piezo1 amplifies cutaneous inflammation by inhibiting autophagy and activating PI3K/AKT signalling to drive M1 macrophage polarization.

Objective and design: We aimed to investigate potential lymphatic vessel abnormalities associated with rosacea and elucidate effective rosacea treatment mechanism using long-pulsed 1064-nm neodymium: yttrium-aluminum-garnet laser (LPND).

Material or subjects: 32 female BALB/c mice were used to established the rosacea-like inflammation model and LPND treatment model. Human lymphatic endothelial cells (HLECs) were used for in vitro studies.

Treatment: LL37 and/or LPND treatment.

Methods: Transcriptomic analyses and clinical observation were performed. Techniques such as Western blotting, immunofluorescence staining, flow cytometry, and clearance assays were employed to assess characteristics of lymphatic vessels. Statistical comparisons between two groups were conducted using Student's t-test or the Mann-Whitney U test, while comparisons among more than two groups were analyzed using one-way or two-way analysis of variance (ANOVA).

Results: Individuals with rosacea exhibited lymphatic dysfunction and LPND treatment could alleviate rosacea-associated clinical edema. Comparative analyses of acute and chronic mouse models revealed lymphatic vessel dilation, reduced density, and impaired function in chronic rosacea-like inflammation. LPND treatment mitigated chronic rosacea-like inflammation by ameliorating lymphatic vessel abnormalities. In vitro experiments demonstrated that LPND attenuated LL-37-induced inflammatory responses in HLECs.

Conclusions: We elucidated the abnormalities of lymphatic vessels in rosacea and provided evidence supporting the targeted lymphatic vessel therapies.

Mitochondrial dysfunction drives Rheumatoid Arthritis (RA) progression by disturbing energy metabolism and promoting inflammation. Additionally, the female predominance of RA highlights estrogen deficiency as an important contributor to disease development. The effect of estrogen in RA has been investigated; however, its specific effects on the mitochondrial proteome and function have yet to be studied. This study investigated the effects of 17-β estradiol (E2) on the mitochondrial proteome of patient-derived RA fibroblast-like synoviocytes (RA-FLS) using Sequential Window Acquisition of all Theoretical Mass Spectra (SWATH-MS) analysis, followed by an assessment of key mitochondrial functional parameters and in vitro validation. The results identified an upregulated expression of two mitochondrial proteins, Acyl-CoA dehydrogenase very long chain (ACADVL) and ATP synthase subunit O (ATP5O), after E2 treatment in RA-FLS. This was further validated by increased real-time ATP production and reduced glycolytic capacity, along with increased expression of proteins related to fatty acid β-oxidation. In addition, E2 influenced mitochondrial dynamics by modulating the fission-fusion balance, resulting in improved mitochondrial morphology. E2 treatment also reduced the expression of mitophagy markers and increased mitochondrial membrane potential, indicating improved mitochondrial function. It also lowered mitochondria-centered oxidative stress by upregulating mitochondrial antioxidant enzymes. Mitochondrial proteomics analysis thus, demonstrated that E2 has the potential to enhance mitochondrial energy metabolism and alleviate mitochondrial dysfunction in RA. These findings provide a foundation for further exploration of mitochondria-targeted therapeutic approaches in RA management.

Objective: To investigate the expression of ferroptosis-related molecules in macrophages of community-acquired pneumonia (CAP) patients and explore their association with disease severity. This study provides novel insights into the role of ferroptosis in CAP pathogenesis by integrating transcriptome sequencing, RT-qPCR, Western blot, and flow cytometry analyses.

Methods: Ferroptosis-related molecules were analyzed in CD14⁺ monocytes and CD11b⁺ macrophages from CAP patients using transcriptome sequencing, RT-qPCR, Western blot, and flow cytometry. Clinical data from CAP patients (n = 46) and healthy controls (n = 63) were compared.

Results: CAP patients exhibited elevated levels of ferroptosis markers (PTGS2, Fe²⁺, and lipid peroxides) and downregulation of inhibitors (TP53 and GPX4). Transcriptome analysis showed activation of the ferroptosis pathway, with significant changes correlating with disease severity. Elevated neutrophil counts and decreased lymphocyte levels were also observed in CAP patients.

Conclusion: Ferroptosis is intricately involved in CAP pathogenesis, with altered expression of key molecules contributing to disease progression. Our findings highlight the potential of targeting ferroptosis-related molecules (e.g., TP53, GPX4, and PTGS2) as a novel therapeutic strategy to mitigate inflammation and tissue damage in CAP. Future studies should validate these findings in larger cohorts.

Emerging evidence indicates that upper and lower airway diseases share anatomical and pathophysiological features. Infections often begin in the upper airway and progress downward, suggesting common immunological mechanisms. Mucin 1 (MUC1), a membrane-bound glycoprotein abundantly expressed in airway epithelial cells, has attracted increasing attention for its immunoregulatory and barrier functions. This review summarizes recent findings on MUC1's involvement in airway inflammation driven by Th1, Th2, and Th17 immune responses. In Th1-type inflammation, MUC1 negatively regulates Toll-like receptor (TLR)-NF-κB signaling pathways, thereby limiting excessive inflammatory responses to bacterial and viral infections. In Th2-type inflammation, MUC1 influences eosinophil survival, maintains epithelial integrity, and modulates glucocorticoid sensitivity, exerting both protective and pathological effects. In Th17-type inflammation, characterized by neutrophil infiltration and elevated IL-17A and IL-22, MUC1 expression alleviates chronic inflammation and may impact microbiome dysbiosis. While MUC1's roles in lower airway disorders are increasingly understood, its specific function and regulatory mechanisms in upper airway diseases remain unclear. This review adopts the unified airway disease (UAD) framework to examine the endotype-specific roles of MUC1 across the upper and lower airways. Rather than providing a disease-by-disease summary, we synthesize evidence through Th1/Th2/Th17 endotypes, link shared mechanisms to biomarker-based patient stratification, and outline MUC1-targeted therapeutic strategies. By applying an endotype- and UAD-centered perspective, the review distinguishes itself from previous work and highlights actionable opportunities for precision medicine. Furthermore, we emphasize the translational potential of MUC1 as both a diagnostic biomarker and a therapeutic target, focusing on advances in small peptides, monoclonal antibodies, RNA interference, and natural compounds that modulate MUC1-related pathways. These developments may ultimately enable the creation of personalized therapies for airway inflammation.

Background and objective: Inflammatory bowel diseases, including Crohn's disease and ulcerative colitis (UC), are chronic conditions characterized by intestinal inflammation. Soluble fiber is fermented by gut microbiota into short-chain fatty acids (SCFA), which possess anti-inflammatory properties. This review aimed to assess the efficacy of oral and topical SCFA administration in patients with UC.

Methods: A systematic review with meta-analysis was conducted in accordance with PRISMA guidelines. Meta-analyses were performed using means and standard deviations to assess clinical and histological outcomes. Endoscopic criteria were also evaluated to determine the effectiveness of the intervention.

Results: Nine studies compared SCFA supplementation with standard therapy, and one employed a crossover design. Oral SCFA, when combined with standard treatment, as associated with reductions in fecal calprotectin and C-reactive protein levels. Meta-analyses of topical SCFA administration revealed a standardized mean difference of - 0.29 ± 0.22, (95% CI: - 0.65 to 0.07; heterogeneity I² = 28%) for the Ulcerative Colitis Disease Activity Index score, and - 0.73 ± 0.61, (95% CI: - 1.58, 0.12; heterogeneity I² = 64%) for histological scores. Endoscopic scores decreased in both intervention and control groups. No adverse effects were observed.

Conclusion: SCFA administration, either orally or topically, has been investigated as a potential adjunct to standard UC therapies. However, the current evidence is limited, particularly for oral administration, which has only been assessed in two studies. Further research is needed to clarify the potential role of SCFA administration.