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关键词： Eosinophilia   tumor necrosis factor-alpha inhibitors   etanercept   golimumab   hematologic side effects   biological  

摘要： Introduction We present an unusual case of a 28-year-old rheumatologic male patient who developed eosinophilia while he was on etanercept therapy first and then on *** Representation Although eosinophilia is rarely reported in the literature as a side-effect of various Tumor Necrosis Factor-alpha [TNF-alpha] antagonists, it represents a riddle about the future treatments of these patients since the persistence of therapy might lead to the onset of dermatologic or visceral eosinophilic complications in such *** Furthermore, the pathogenesis of eosinophilia is still unknown, and all the proposed hypotheses do not explain the eosinophilic proliferation in certain subjects.

关键词： Intervertebral disc degeneration   BQU57   Inflammation   Apoptosis   NF-kappa B signaling pathways  

摘要： Background: Intervertebral disc degeneration (IVDD) is a significant contributor to lower back pain (LBP), affecting approximately 80 % of the global population. The RalA inhibitor BQU57 plays a role in various cellular functions;however, its impact on nucleus pulposus cell (NPC) degeneration remains unclear. Methods: This study employed a combination of bioinformatics analysis and experimental validation to investigate the role of RalA in IVDD and its inhibitor BQU57 in its therapeutic potential. Gene expression datasets from the GEO database were analyzed to identify genes associated with IVDD, and clinical intervertebral disc samples were collected to validate the upregulation of RalA in degenerated discs. In vivo and in vitro assessments were conducted to evaluate the effects of BQU57 on the extracellular matrix (ECM) metabolism and apoptosis of nucleus pulposus (NP) cells. Results: Elevated expression of RalA was observed in degenerated intervertebral discs from IVDD patients, and its expression was correlated with disease severity. Further mechanistic studies revealed that the RalA inhibitor BQU57 could balance ECM metabolism and apoptosis, potentially through the activation of the NF-kappa B signaling pathway. Conclusion: RalA plays a significant role in the pathogenesis of IVDD, and it may serve as a novel therapeutic target for IVDD. BQU57 demonstrates potential as an effective small molecule drug for the prevention and treatment of IVDD.

关键词： Achilles tendon regeneration   Piezoelectric PCL/BTO nanofilm   Macrophage and T cells   Immunomodulation   IL-17A/NF-kappa B signaling pathway  

摘要： Tendon injuries are often exacerbated by persistent inflammation, which hampers tissue regeneration. In this study, we developed a noninvasive, wirelessly controlled, and self-powered piezoelectric nanofilm fabricated by coaxial electrospinning of polycaprolactone (PCL) and tetragonal barium titanate nanoparticles (BTO), and investigated its roles in modulating inflammation and repairing Achilles tendon defects as well as the mechanism in a rat model. In vitro study and in vivo study upon subcutaneous implantation showed that the piezoelectric PCL/BTO nanofilms could inhibit M1 macrophage polarization and reduce the secretion of inflammatory factors. Moreover, when bridging an Achilles tendon defect, the nanofilms could promote tenogenic gene expression including collagen deposition, and collagen remodeling, facilitate functional tendon recovery and significantly reduce tissue inflammation by suppressing M1 macrophage polarization and promoting M2 polarization. Moreover, the piezoelectric stimulation could also enhance tendon regeneration by inhibiting angiogenesis, reducing lipid deposition, and decreasing ectopic ossification. Mechanistically, the piezoelectric nanofilms reduced tissue inflammation mainly via inhibiting the nuclear factor (NF)-kappa B signaling pathway that is mediated by interleukin (IL)-17A secreted from CD3+ T cells, and thus to reduce proinflammatory factors, such as IL-1 beta and IL-6, inducible nitric oxide synthase, monocyte chemoattractant protein-1, and tumor necrosis factor-alpha. These findings indicate the potential of piezoelectric stimulation in immunomodulation, and in promoting tendon regeneration via IL-17A/NF-kappa B-mediated pathway.

关键词： Psoriasis   Arthritis   Gut microbiota   Interleukin 17   Carbohydrate-Active enZymes  

摘要： Objectives: To explore the evolution of gut microbiota in taxonomy and function in PsA patients during IL-17i treatment. Methods: Twenty PsA patients treated with secukizumab were included. Fecal samples were collected before treatment (0 mo.), first month (1 mo.) and third month (3 mo.) after treatment, and a total of 60 samples were collected. Shotgun metagenomic sequencing was used to detect all fecal samples. Results: In the 1 mo. and 3 mo. after IL-17i treatment, the disease activity in PsA patients decreased significantly. Compared with 0 mo., alpha-diversity calculated by Shannon index and Pielou index increased significantly at 1 mo. and 3 mo. after treatment. Microbial genes encoding Carbohydrate-Active enZymes (CAZymes) tended to be upregulated after treatment. After treatment, Bacteroidota phylum expanded, especially the abundance of Phocaeicola genus increased gradually with the treatment time (P < 0.05). The abundance of Phocaeicola genus was positively correlated with the alpha-diversity. The Polysaccharide Lyases and Carbohydrate Esterases in CAZymes were significantly positively correlated with most of species in Phocaeicola genus. Conclusions: Treatment with IL-17i induces gut microbiota evolution in PsA patients. The key features of this evolution include increased alpha-diversity, expansion of the Phocaeicola genus, and upregulation of CAZymes. Species within the Phocaeicola genus may be the critical bacteria driving this evolution. (c) 2025 Socioto Franoaise de Rhumatologie. Published by Elsevier Masson SAS. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

关键词： Psoriatic arthritis   TNF-a inhibitor   Flare   Tapering   Ultrasonography  

摘要： Objective: Dose reduction of biologic drugs in patients with psoriatic arthritis (PsA) who are in Minimal Disease Activity (MDA) is now considered a feasible option. This study evaluated which baseline clinical and ultrasonographic (US) factors may be predictive of disease activity after anti-TNF-a spacing. Methods: This observational, prospective, multicentre, 12-month study enrolled consecutive adult patients with PsA taking TNF-a inhibitors and in stable MDA who accepted to reduce their dose therapy by doubling the administration interval. Data collection included demographics, personal history, clinical disease characteristics, and joints and entheses US features. Patients maintaining the MDA were compared with those who experienced a disease flare during the 12 months of follow-up. The statistical analysis included the comparison between groups and the search of the factors associated with persistence of MDA. Results: Of the evaluable 72 patients (29 females and 43 males), 55 (76.4%) maintained a state of MDA while 17 (23.6%) experienced a disease relapse. Baseline values of DAPSA<2 and of BASDAI<1.5, and lower BASDAI and DAS28 values were significantly associated with maintenance of MDA. The multivariate analysis showed that baseline values of DAPSA< 2 and of BASDAI < 1.5 were predictive of persistence of MDA. Baseline US findings were not associated with the outcome of disease activity. Conclusions: In this study, anti-TNF-a spacing proved to be feasible in most of the PsA patients in a stable MDA. The only factor predictive of persistence of remission was a very low clinical disease activity at baseline. (c) 2025 Socioto Fran oaise de Rhumatologie. Published by Elsevier Masson SAS. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

关键词： Inflammation   Immune epilepsy   Cytokines   Ghrelin  

摘要： Purpose: This study aimed to investigate the relationship between ghrelin levels and severity of inflammation in children with epilepsy by evaluating the differences in total ghrelin, High Mobility Group Box 1 (HMGB1), Interleukin-1 Receptor Type 1 (IL1R1), and Interleukin-1 Beta (IL1-beta) levels in patients with drug-resistant and non-drug-resistant epilepsy and comparing these parameters with those of healthy controls. Methods: We measured total ghrelin, HMGB1, IL1R1, and IL1-beta levels-known to play roles in epileptogenesis-in patients with severe (n: 28), mild (n:29) epilepsy, and 31 healthy controls. The severe epilepsy group included patients with treatment-resistant epilepsy, while the mild epilepsy group consisted of patients whose seizures could be controlled with monotherapy. Results: Total ghrelin levels, along with HMGB1, IL1R1, and IL1-beta, were significantly elevated in children with epilepsy compared to healthy controls. This increase was more pronounced in the drug-resistant epilepsy group, suggesting a potential role for ghrelin in drug-resistant epilepsy. While no direct correlation was found between ghrelin and the inflammatory markers, we observed that ghrelin levels rose significantly when levels of IL1R1, IL1-beta, and HMGB1 surpassed their respective cut-off values in epilepsy patients. The biomarkers IL1R1 and IL1-beta had the strongest discriminative potential in distinguishing patients with severe epilepsy from healthy controls. Although ghrelin was not as powerful a diagnostic marker as IL1R1 or IL1-beta, it still showed moderate diagnostic value. Conclusion: Ghrelin could serve as a biomarker reflecting both inflammation and drug resistance in epilepsy. It may be associated with inflammatory responses in epilepsy and could play a potential role in the pathophysiology of the disease.

关键词： Systemic lupus erythematosus   Double-negative T cells   Interleukin-10 signaling pathway   SLE disease activity index   RNA sequencing   Autoantibodies  

摘要： Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that causes immune system overactivity and organ damage. Among T-cell subsets involved in SLE, CD4 and CD8 double-negative alpha beta T (DNT) cells have attracted attention in recent years, although their role in SLE remains poorly understood. Examining the minute intricacies, particularly signaling pathway modifications is crucial, as it may unveil potential therapeutic targets and lead to the development of more effective treatments. Our study found increased DNT cells in pediatric SLE patients, with elevated IL-10 signaling. These IL-10-producing DNT cells were positively related to disease activity defined by SLE Disease Activity Index (SLEDAI), and were further elevated in patients with lupus nephritis. Additionally, our results indicated that IL-10-producing DNT cells correlated positively with anti-Sm autoantibodies. Collectively, our study revealed that modulation of IL-10 production within DNT-cell subset could affect both immune regulation and autoantibody production, contributing to the immunological dysregulation in SLE.

关键词： ADAM12   DNA damage response   GBM   TMZ   TNF-α  

摘要： Development of temozolomide (TMZ) resistance is a critical factor contributing to a poor prognosis in glioma patients. TMZ resistance is also closely associated with the phosphorylation level of NF-κB, yet targeted inhibition of NF-κB activity in glioma can be leveraged to overcome TMZ resistance. ADAM12, a protein significantly overexpressed in glioma cells, is implicated in the pathogenesis and progression of glioma, yet its role in the development of TMZ resistance is completely understood. We found that knockdown of ADAM12 was shown to arrest the glioma cell cycle, enhance apoptosis, inhibit DNA damage repair mechanisms, and sensitize glioma cells to TMZ. Targeting ADAM12 in vivo was found to increase the sensitivity of glioma cells to TMZ. Survival analysis indicated that ADAM12 serves as a prognostic marker for TMZ treatment. Using ELISA and protein interaction predictions via docking simulation, we identified the TNF-α shedding function of ADAM12 as a critical regulator of glioma progression. Furthermore, in glioma cell lines with unmethylated MGMT, the knockdown of ADAM12 enhanced sensitivity to TMZ by inhibiting the TNF-α/NF-κB pathway and reducing MGMT expression. In all, these results demonstrated that ADAM12 aids in shedding of membrane-bound TNF-a to drive TMZ resistance in glioma. © 2025 Elsevier B.V.

关键词： Red nucleus   Neuropathic pain   Metabotropic glutamate receptors   Tumor necrosis factor-alpha   Interleukin-1 beta  

摘要： Metabotropic glutamate receptors (mGluR) participate in pain modulation and mediate different effects in nociceptive stimuli, relying on the receptor subtype activated and its anatomical location. Here, we addressed the functions of mGluR III group (mGluR4, mGluR6, mGluR7, and mGluR8) in the red nucleus (RN) in nociception and the development of neuropathic pain induced by spared nerve injury (SNI) using male rats. Our results showed that mGluR4, mGluR7, and mGluR8, except for mGluR6, were constitutively expressed in the RN of normal rats. At 2 weeks post-SNI, the expressions of mGluR4 and mGluR8 rather than mGluR7 were reduced in the RN contralateral to the nerve lesion. Unilateral administration of mGluR III antagonist MSOP to the RN of normal rats decreased the PWT of contralateral hindpaw and evoked pronounced mechanical allodynia, which was blocked by mGluR4 agonist VU0155041 or mGluR8 agonist AZ12216052 instead of mGluR7 agonist AMN082. Moreover, administration of VU0155041 or AZ12216052 to the RN contralateral to the nerve injury at 2 weeks post-SNI alleviated SNI-induced neuropathic pain. Further studies indicated that administration of MSOP to the RN of normal rats increased the expressions of nociceptive factors TNF-alpha and IL-1 beta, which were blocked by VU0155041 or AZ12216052 instead of AMN082. Additionally, administration of VU0155041 or AZ12216052 to the RN at 2 weeks post-SNI inhibited the overexpressions of TNF-alpha and IL-1 beta induced by SNI. These findings suggest that red nucleus mGluR4 and mGluR8 instead of mGluR7 inhibit nociception and the development of neuropathic pain by restraining the expressions of TNF-alpha and IL-1 beta.