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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： anti-TNF drug levels   transcriptomics   microRNA   Crohn's disease   gene regulation  

摘要： Background MicroRNAs (miRNAs) play a key role in regulating gene expression in Crohn's disease (CD). Although several studies have identified miRNAs with biomarker potential, an exhaustive characterization of the miRNAome in CD is still lacking. We performed the largest miRNA profiling effort to date to analyze miRNA variability across intestinal tissues, disease activity status, and infliximab treatment in *** We generated 119 transcriptomic profiles from the terminal ileum and left colon biopsies of 30 individuals (10 with active CD, 10 with quiescent CD, and 10 healthy controls). Half of the samples were cultured ex vivo with infliximab, and the remaining half with basal medium. Using variance analyses and linear mixed differential expression models, we explored the determinants of miRNAome variability in CD. We also generated infliximab response signatures to identify candidates and examine interactions between miRNAs and the coding *** Tissue location, and patient-specific effects, were the main factors in miRNA variability in CD, with some differentially expressed miRNAs involved in epithelial-mesenchymal transition (miR-200s, miR-429). We identified 9 miRNAs with treatment-responsive behaviour, particularly to the terminal ileum of active CD cases. Although the changes observed in active CD cases suggest that many alterations are not offset by infliximab incubation, we described 13 miRNAs-mRNA pairs with potential involvement in the anti-tumor necrosis factor (TNF) treatment, 7 of which have been already *** A comprehensive miRNA profiling revealed significant intestinal tissue-specific variability and identified key alterations in the miRNA-mRNA interactome that might be involved in therapeutic response to anti-TNF in CD. This article provides an extensive characterization of the miRNA variability in Crohn's Disease biopsies incubated ex vivo with infliximab, revealing tissue-specific regulatory programs and identif

关键词： Adenosine   Cytokine   T cell   Immunosuppression  

摘要： Background Adenosine accumulated in the tumor microenvironment functions as an immune-modulating factor, exerting immunosuppressive actions via adenosine A2A/A2B receptor (A2AR/A2BR) in various immune cell types. CD73, a key enzymatic regulator responsible for adenosine production, is frequently overexpressed in diverse cancers, and its overexpression is associated with reduced responsiveness to conventional anti-cancer drug treatments such as chemotherapy, radiation therapy, targeted therapy, or immunotherapy. Despite numerous therapeutic applications of IL-2 in cancer immunotherapy, the relationship between the CD73-adenosine axis and IL-2-based immunotherapy remains largely *** To evaluate the effect of CD73 blockade on IL-2 signaling of CD8+ T cells, we screened novel CD73 antibodies using human single-chain variable fragment phage library and immunized Alpaca phage library. To optimize targeting to CD73-expressing cells and reinvigorate the antitumor effect of IL-2 in adenosine-rich microenvironment, we engineered a novel bifunctional GI-alpha CD73/IL-2v fusion protein. Functionality of GI-alpha CD73/IL-2v fusion protein was assessed in the in vitro cell-based assays and the in vivo tumor-bearing mouse model or cynomolgus *** IL-2-induced increase in proliferation of CD8+ T cells was not observed under adenosine-rich microenvironment. We demonstrated that the functional impairment of IL-2 signaling in CD8+ T cells in these conditions can be reversed by our anti-CD73 antibody (GI-alpha CD73). Furthermore, GI-alpha CD73/IL-2v fusion protein significantly restored the impaired proliferation of CD8+ T cells and consequently enhanced tumor cell killing under adenosine-mediated immunosuppression, surpassing the combined treatment of GI-alpha CD73 and Fc-IL-2v. These synergistic effects were attributed to the enhanced delivery of the IL-2v component of GI-alpha CD73/IL-2v to IL-2R beta gamma on CD73-expressing CD8+ T cells through a cis-bindi

关键词： Doxorubicin   Interleukin-17A   Secukinumab   Nuclear factor kappa beta   Pyrin domain containing 3   Interleukin-1 beta  

摘要： Doxorubicin (DOX) is used as a chemotherapeutic drug for treating cancer. Nevertheless, it causes damage to the heart by activating inflammatory pathways, resulting in cardiotoxicity. Imbalance in cytokine production is a crucial component that might trigger the initiation of inflammatory processes. Inflammatory cytokines could be targeted therapies against cardiovascular diseases (CVDs). Interleukin-17A (IL-17A) is a cytokine that promotes inflammation and stimulates harmful immunological reactions. The objective of the study was to determine the efficacy of secukinumab (SEC), a completely human monoclonal IgG1/kappa antibody that targets IL-17A, in ameliorating DOX-induced cardiotoxicity (DIC). We administered 2.5 mg/kg of DOX intraperitoneally to male Wistar rats three times a week for 2 weeks and simultaneously administered 0.9 mg/kg of SEC along with 2.5 mg/kg of DOX injection three times a week for a duration of two weeks. The findings indicated that DOX induced damage to the heart tissue, resulting in a significant rise in indicators of cardiotoxicity (P < 0.001), as well as oxidative stress and inflammation. DIC may have arisen from DOX's activation of the Pyrin domain containing 3 (NLRP3) inflammasome and the nuclear factor kappa beta (NF-kappa B) pathway. The co-administration of SEC successfully reversed all DOX-induced abnormalities by restoring cardiac functions to their baseline levels, decreasing levels of inflammatory mediators such as IL-17A and interleukin-1 beta (IL-1 beta), and improving oxidative stress by reducing levels of malondialdehyde (MDA) and increasing levels of reduced glutathione (GSH). Furthermore, it mitigated the heightened activation of the NF-kappa B/NLRP3 pathway caused by DOX. This study shows that IL-17A neutralization can prevent DIC by regulating the NF-kappa B/NLRP3/Caspase-1/IL-1 beta pathway to be used as potential therapeutic target for CVDs.

关键词： cathepsin B   cathepsin L   human gingival fibroblast   interleukin-6   caveolin  

摘要： Aims Cathepsins are essential lysosomal enzymes that maintain organismal homeostasis by degrading extracellular substrates. The inflammatory cytokine interleukin-6 (IL-6) increases the production of cathepsins through the caveolin-1 (Cav-1) and c-Jun N-terminal kinase (JNK) signaling pathways, which have been implicated in the destruction of periodontal tissue. This study investigated the effect of the IL-6/soluble IL-6 receptor (sIL-6R) complex on the extracellular secretion of cathepsins in human gingival fibroblasts (HGFs) and examined the function of extracellularly secreted cathepsins B and L under acidic culture conditions in *** HGFs were isolated from healthy volunteer donors. The expression of Cav-1 was suppressed via transfection with small interfering RNA (siRNA) targeting Cav-1. The expression levels of cathepsins B and L induced by extracellular IL-6/sIL-6R were measured using western blotting and enzyme-linked immunosorbent assay. Extracellular cathepsin activity following IL-6/sIL-6R stimulation was assessed using a methylcoumarylamide substrate in a fluorescence-based assay. IL-6/sIL-6R-induced expression of cathepsins B and L in HGFs was quantified under inhibitory conditions for extracellular signal-regulated kinase (ERK) 1/2 and/or JNK signaling, both of which are transduction pathways activated by IL-6/sIL-6R. This quantification was also performed in HGFs with suppressed Cav-1 expression using western *** Cathepsins B and L were secreted in their precursor forms from HGFs, with significantly elevated protein levels observed at 24, 48, and 72 h post-IL-6/sIL-6R stimulation. Under acidic culture conditions, cathepsin B activity increased at 48 and 72 h. Cav-1 suppression inhibited the secretion of cathepsin B regardless of IL-6/sIL-6R stimulation, whereas the secretion of cathepsin L was reduced only after 48 h of IL-6/sIL-6R stimulation. Inhibition of ERK1/2 and JNK pathways decreased the secretion of cathepsin B after 48 h

关键词： metabolic syndrome   insulin resistance   Mini-Mental State Examination   MMSE   inflammation   cognitive function  

摘要： Background: Metabolic syndrome (MetS) and related disorders, such as insulin resistance, pose significant health risks in middle-aged women, including cognitive decline. Chronic inflammation, characterized by elevated levels of interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha), has been identified as a key mechanism linking metabolic disturbances to neurodegenerative processes. Methods: This study aimed to examine the associations between metabolic disorders, inflammatory markers, and cognitive function among middle-aged women. A cross-sectional study was conducted on 179 non-smoking perimenopausal and postmenopausal women aged 43-73 years. Anthropometric, metabolic, and cognitive parameters were assessed, including body mass index (BMI), waist-to-height ratio (WHtR), fasting glucose (GLU), triglycerides (TG), IL-6, TNF-alpha, and Mini-Mental State Examination (MMSE) scores. Logistic regression models were applied to evaluate the relationships between inflammation, MetS components, and cognitive impairments. Results: Women with insulin resistance showed significantly worse metabolic profiles and lower MMSE scores (23.98 vs. 24.91, p = 0.032). IL-6 levels were strongly associated with hypertriglyceridemia (OR = 1.096, 95% CI: 1.044-1.151, p < 0.001) and insulin resistance (OR = 1.068, 95% CI: 1.030-1.107, p < 0.001), while TNF-alpha correlated with abdominal obesity (WHtR OR = 1.429, 95% CI: 1.005-2.031, p = 0.047). Moreover, TNF-alpha was a significant predictor of cognitive impairments (OR = 1.362, 95% CI: 1.153-1.610, p < 0.001), whereas IL-6 showed no significant association. Conclusions: These findings highlight that TNF-alpha may be a key inflammatory marker associated with metabolic disturbances and cognitive decline in middle-aged women. IL-6 appears to be more specifically linked to lipid abnormalities and insulin resistance. Targeted interventions to reduce inflammation may moderate metabolic and cognitive risks in this population.

摘要： gamma delta T cells represent key players in immune surveillance after T-cell receptor alpha/beta (alpha beta)/CD19depleted HLA-haploidentical hematopoietic stem cell transplantation (haplo-HSCT). Although encouraging data are available on the impact of V delta 2-targeting therapy in improving HSCT clinical outcomes, their role in providing antimicrobial immunity is largely unexplored. This study aimed to investigate the antiviral protective profile of V delta 2 T cells in pediatric patients given haplo-HSCT. The characterization of gamma delta T cells was performed in pediatric recipients (n = 26) in the donor graft and at 30, 60, and 120 days after haplo-HSCT. The antiviral activity of V delta 2 T cells and the cytomegalovirus (CMV)-specific alpha beta T-cell immunity was analyzed. Early after HSCT, V delta 2 T cells was significantly higher in patients who did not experience viral reactivation (No-VR) than in patients with CMV reactivation. Interestingly, this difference was already present in the grafts. Clustering analysis identified a protective subset of V delta 2 T cells in patients with No-VR, expressing CD16, NKG2D, and CD107a, and producing Th1 cytokines. This subset directly correlated with interleukin-15 and inversely with the CMV DNA level. Stimulated V delta 2 T cells inhibit CMV replication, acquired CD86/HLA-DR molecules, induced HLA-DR on monocytes, and improved the alpha beta CMV-specific T-cell response. Altogether, these results identify an antiviral protective profile displayed by V delta 2 T cells early after HSCT, and define their ability to inhibit CMV replication, to induce antigen-presenting cell maturation and to improve alpha beta virus-specific T-cell response, opening a new application of V delta 2-targeting immunotherapy after HSCT, adding the antiviral to the antitumor potential.