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关键词： Collagen VII   Cytokines   Fibrosis   IL-1   Pseudosyndactyly  

关键词： ferroptosis   glycolysis   HIF-1 alpha   IL-10R alpha   MOF   osteoarthritis  

摘要： Osteoarthritis (OA) is a low-grade inflammatory disease that is highly associated with severe hyperplasia of the synovial membrane and the degeneration of cartilage. Interleukin-10 (IL-10), has been extensively studied, while its receptor, IL-10R alpha, has not been widely mentioned in the context of OA. A significant difference is found in the expression of IL-10R alpha in synovial macrophages from normal and OA patients, along with a marked increase in the glycolytic activity of synovial macrophages. In IL-10R alpha Lysm OA mice, the specific deficiency of IL-10R alpha exacerbated the progression of OA. Mechanistically, hypoxia-inducible factor-1 alpha (HIF-1 alpha) is identified as a key transcription factor, and its inhibition significantly weakened the glycolytic process. Additionally, differences in ferroptosis of chondrocytes are observed. After co-culturing the two types of cells in vitro, a significant connection is found between the glycolytic state of synovial macrophages and the ferroptosis of chondrocytes. To achieve targeted therapy, MI@UN, a biomimetic nanoparticle encapsulating NO-prednisolone in UIO-66-NH2, surface-modified with IL-10, and coated with macrophage membranes (MM), is developed. It significantly slows osteoarthritis progression in mice. This offers new insights into OA pathogenesis, highlighting IL-10R alpha as a therapeutic target and supporting MI@UN's translational use for OA treatment.

关键词： Diabetic kidney disease   Hypoxia   Sirt1   Hif-1(   Morusin  

摘要： Background and Purpose: Hypoxia is generally considered the major cause of renal tubular injury. The interaction between sirtuin 1 (SIRT1) and hypoxia inducible factor 1 subunit alpha (HIF-1 alpha) is a key mediator of hypoxiainduced renal tubular damage. In this study, we identified morusin from a screen of SIRT1 inducers and reported its potential for the treatment of diabetic kidney disease (DKD). Experimental Approach: Intraperitoneal injection of morusin in db/db and STZ-induced diabetic mice was assessed for its effect on tubulointerstitial damage. The expression and acetylation level of HIF-1 alpha were analyzed by immunoblotting or immunostaining. The effects of morusin treatment on hypoxia-induced extracellular matrix (ECM) accumulation, apoptosis and IL-16 production in HK2 cells were evaluated by immunoblotting. Luciferase reporter gene and ChIP analysis was used to determine whether IL-16 was the target genes of HIF-1 alpha. Key Results: In db/db and STZ-induced mice, morusin treatment alleviated kidney injury and inhibited renal inflammation and fibrosis. Mechanistic analysis using animal models and HK2 cells revealed that morusin treatment upregulated SIRT1 expression by enhancing its stability, and reduced the expression and acetylation levels of HIF-1 alpha as well as expression of its regulated genes, thereby inhibiting ECM accumulation, apoptosis and IL-16 production. Furthermore, morusin decreased expression of the IL-16 through inhibited HIF-1 alpha binding to the IL-16 promoter. Conclusion and Implications: Our study is the first to demonstrate that morusin ameliorated tubulointerstitial damage in diabetic mice by regulating SIRT1/HIF-1 alpha/IL-16 signaling pathway. Taken together, our findings suggest that morusin is a clinical candidate compound to prevent DKD.

关键词： Ionic liquids   Microwave Irradiation   Solvents   Additives   Nanomaterials  

摘要： The synergy between ionic liquids (ILs) and microwave (MW) irradiation has sparked a significant interest in material synthesis in general and nanomaterials in particular, revolutionizing the field of materials science. This review explores the fundamental properties and unique attributes of ILs, emphasizing their role as solvents, additives, templates, making them ideal for synthesizing materials, particularly nanomaterials like metals, metal oxides, and doped nanoparticles. The microwave assisted synthesis approach is discussed next vis-& agrave;-vis their advantages such as volumetric heating, reduced reaction times, enhanced yields and facile scalability. A new synthetic approach is also expounded on, where in very small quantity of an ionic liquid (IL), as an additive, can be coupled with low heating microwave solvents (non-polar solvents) and subjected to microwave-irradiation. The new strategy of Ionic-liquid (IL) Mediated Microwave Synthesis (ILMMAS), can be particularly important in nanomaterial synthesis, as the non-polar solvents can be heated very quickly under microwave irradiation. This review emphasizes the crucial role of ILs in advancing nanomaterial synthesis and highlights their synergy with microwave irradiation for sustainable and efficient material synthesis processes.

关键词： HLA-C   nanotype sequencing   null allele   sequencing-based typing  

摘要： The novel HLA-C*08:307 N allele has a four-nucleotide insertion in exon 2.

关键词： Interleukin-6   Circadian rhythms   Metabolic cycles   Energy balance   Sexual dimorphism  

摘要： Objective: Interleukin-6 (IL-6) is a pleiotropic cytokine involved in immune regulation and energy metabolism. Its diurnal secretion influences core circadian components, emphasizing its critical role in circadian biology. Despite known sex differences in immune, circadian, and metabolic processes, how IL-6 integrates these processes remains poorly understood. Methods: IL6 knockout (KO) and control mice of both sexes were phenotyped for circadian and metabolic traits under standard (STD) and high-fat diet (HFD), fasting, and time-restricted feeding. Molecular analyses in muscle, liver, and hypothalamus assessed clock gene expression and IL-6 signaling pathway. Circulating sex steroid hormones were quantified to examine their contribution to the observed sex-specific phenotypes. Results: IL-6 deficiency disrupts circadian locomotor and metabolic rhythms in a sex-and diet-dependent manner. Males exhibit impaired light-driven circadian rhythms under STD conditions and metabolic misalignment under HFD, whereas females display greater circadian resilience under STD conditions but increased vulnerability to circadian disruption during HFD. Additionally, IL-6 emerges as a novel regulator of the foodentrainable oscillator (FEO), linking food anticipatory activity and metabolic cycles under both STD and HFD in a sex-dependent manner. Conclusions: These findings identify IL-6 as a critical mediator of circadian-metabolic plasticity, shaping sex-and diet-specific trade-offs between circadian stability and metabolic homeostasis. Our study highlights IL-6 as a potential therapeutic target for mitigating circadian misalignment-associated metabolic disorders, with implications for the timed modulation of IL-6 signaling. (c) 2025 The Authors. Published by Elsevier GmbH. This is an open access article under the CC BY-NC-ND license (http://***/licenses/by-nc-nd/4.0/).

关键词： cell contact   chemokines   mesenchymal stem/stromal cells   paracrine factor   type 1 diabetes mellitus  

摘要： Interferon-gamma (IFN gamma) plays a crucial role in the pathogenesis of type 1 diabetes (T1D) and is widely utilized to license mesenchymal stem/stromal cells (MSCs) to enhance their immunosuppressive properties through a process known as preconditioning or priming. This study investigates the interaction of MSCs preconditioned with (IFN gamma+) or without (IFN gamma-) IFN gamma, with peripheral blood mononuclear cells (PBMCs) from healthy controls (HC) and T1D patients. We assessed the effects of these interactions on anti-inflammatory gene expression, chemokine and receptor profiles, and the induction of regulatory T (Treg) cells. Our findings reveal contrasting responses in HC and T1D PBMCs when exposed to IFN gamma+ and IFN gamma- MSCs, particularly in the expression of key genes such as CXCR3 and its ligands (CXCL9, CXCL10), CXCR6, CCR5, and its ligands (CCL3 and CCL4). Pathway enrichment analysis further showed that IFN gamma preconditioning tailors MSC responses to specific immune microenvironments. These differential gene expression patterns were also reflected in the proportions of Treg cells, which varied depending on whether paracrine signaling or direct cell contact was involved. Collectively, our results demonstrate that IFN gamma+ and IFN gamma- MSCs create distinct immunomodulatory microenvironments in T1D PBMCs compared to HC PBMCs, emphasizing the potential for tailored MSC-based therapies in T1D treatment.

关键词： Host resistance   Haemonchus contortus   Cytokine   Gene expression   Garole sheep  

摘要： Role of IFN-gamma and IL-10 cytokines and associated genes (IFN-gamma and IL-10) on Haemonchus contortus resistance was studied in experimentally infected resistant and susceptible Garole sheep. Nine resistant and nine susceptible Garole sheep were selected based on faecal egg counts (FEC) and divided into 3 groups;uninfected control (n = 6), infected resistant (n = 6) and infected susceptible (n = 6). Sheep of infected groups were orally challenged with 500 H. contortus infective larvae per kg body weight of experimental sheep. Faecal egg counts were measured from 18 days post infection (DPI) at 3 days intervals for nine occasions, and plasma cytokines (IFN-gamma and IL-10) concentration and expressions of cytokine genes (IFN-gamma and IL-10) expressions were measured from 0 DPI to 40 DPI at 10 days intervals. Resistant sheep had significantly (P < 0.001) lower FEC from 27 DPI onwards compared to susceptible sheep and subsequently no eggs were found in resistant sheep from 33 DPI onwards. In resistant sheep, significantly higher concentration of IFN-gamma cytokine and expression of IFN-gamma gene were observed at early stage (10-20 DPI), and IL-10 cytokine production and IL-10 gene expression upregulated at later stage of infection (20-30 DPI) after which there was significant reduction of egg output in faeces of resistant group of sheep. Hence in Garole sheep both the IFN-gamma and IL-10 cytokines and their associated genes might be linked with H. contortus resistance with IL-10 cytokine gene playing comparatively more active role in development of resistance to H. contortus.