Search Results (26,326)

Ionic liquids (ILs) have attracted considerable attention for light olefin separation owing to their negligible vapor pressure, excellent thermal stability, and tunable molecular structures. However, their intrinsically high viscosity severely restricts gas diffusion, leading to poor mass-transfer efficiency and limited separation performance in bulk form. Herein, we report the develop a high-performance adsorbent by immobilizing a silver-functionalized ionic liquid within ordered mesoporous MCM-41 to overcome the diffusion limitations of bulk ILs. The IL@MCM-41 composites were prepared via an impregnation–evaporation strategy, and their mesostructural integrity and textural evolution were confirmed by XRD and N₂ sorption analyses. Their C₂H₄/C₂H₆ separation performance was subsequently evaluated. The composite with a 70 wt% IL loading achieves a high C₂H₄ uptake of 25.68 mg/g and a C₂H₄/C₂H₆ selectivity of 15.59 in breakthrough experiments (298 K, 100 kPa). X-ray photoelectron spectroscopy results are consistent with the presence of reversible Ag⁺–π interactions, which governs the selective adsorption of C₂H₄. Additionally, the composite exhibits excellent thermal stability (up to 570 K) and maintains stable separation performance over 10 adsorption–desorption cycles. These IL@MCM-41 composites have significant potential for designing sorbent materials for efficient olefin/paraffin separation applications. Full article

Ziziphus jujuba is an important source of polysaccharides in food supply, and studies have demonstrated that polysaccharides serve as the principal active constituents responsible for immunomodulatory effects. The results indicated that “Huizao” polysaccharides (HP2-1) increased the viability and phagocytic activity of RAW264.7 cells and triggered immune responses by promoting cytokines TNF-α, IL-6, and IL-1β secretion, as well as NO and ROS production. In addition, HP2-1 also stimulated cytokine production, elevated immunoglobulin levels, and alleviated oxidative stress via increasing antioxidant enzyme activities and reducing MDA production in immunosuppressed mice. Furthermore, HP2-1 potentiated immune responses both in vitro and in vivo by modulating the TLR4/MAPK/NF-κB pathway due to upregulating TLR4 expression, leading to phosphorylation of ERK, JNK, and p38 MAPKs, thereby activating NF-κB and subsequent cytokine secretion. Full article

Chronic diabetic wounds are characterized by persistent inflammation, impaired angiogenesis, oxidative stress, and defective tissue remodeling, leading to delayed healing. Cordyceps militaris, a medicinal fungus with known anti-inflammatory and antioxidant properties, has shown therapeutic potential in metabolic disorders; however, its role in diabetic wound repair remains unclear. In this study, we evaluated the wound-healing effects of an aqueous extract of C. militaris using in vitro keratinocyte models and a streptozotocin-induced diabetic mouse model. C. militaris treatment significantly accelerated wound closure, improved epidermal regeneration, and enhanced skin barrier integrity. Mechanistically, C. militaris restored HIF-1α and TGF-β1 expression, promoted cell proliferation and fibroblast activation, and increased the expression of matrix metalloproteinases MMP-1 and MMP-2, indicating enhanced extracellular matrix remodeling. In parallel, excessive inflammatory responses were attenuated, as evidenced by reduced IL-6 and TNF-α levels, along with activation of SIRT1/Nrf2/HO-1 antioxidant signaling pathways. Collectively, these findings demonstrate that C. militaris promotes a balanced wound-healing microenvironment and represents a promising natural therapeutic candidate for the treatment of diabetic wounds. Full article

Brown algae of the Cystoseira genus are recognized as valuable sources of bioactive compounds, including polysaccharides. Within the framework of current restoration efforts regarding damaged Ericaria amentacea populations in the Mediterranean Sea, the valorization of apices derived from ex situ cultivation waste represents a sustainable opportunity for industrial and biomedical applications. In this study, sodium alginate (SA) was extracted from E. amentacea apex by-products using a hydrothermal–alkaline method and subsequently chemically characterized. FTIR analysis showed O-H, C-H, and COO- stretching compatible with commercial alginates, while 1H-NMR spectroscopy indicated high β-D-mannuronic acid content, with an M/G ratio of 2.33. The extracted SA displayed a molecular weight of 1 × 10⁴ g/mol and a polydispersity index of 3.5. The bioactive properties of the SA extract were investigated in chemico and in vitro. SA exhibited remarkable antioxidant activity, showing significant DPPH and nitric oxide-radical-scavenging capacity. Furthermore, SA demonstrated a strong anti-inflammatory effect in LPS-stimulated macrophages through modulation of several inflammatory mediators (i.e., IL-6, IL-8/CXCL5, MCP-1, and TNF-α). In particular, SA promoted a striking iNOS gene expression inhibition, which, paired with its direct NO-scavenging ability, paves the way for future pharmacological use of E. amentacea derivatives, particularly if sustainably obtained from restoration activity waste. Full article

Acute lung injury may occur after cardiac arrest (CA), with innate immunity likely playing an important role in lung inflammation after CA. This study aimed to survey serial changes in the toll-like receptor (TLR) 4 signaling pathway in post-resuscitation lung injury in CA rats. A randomized animal study was conducted in rats with CA followed by successful cardiopulmonary resuscitation (CPR). The expression of TLR4 pathway biomarkers was analyzed and compared to the sham controls at different time points after CA with CPR. Lung tissues were collected for histological analysis to assess structural damage. Bronchoalveolar lavage fluid (BALF) was analyzed to quantify inflammatory cytokines and to assess changes in regulatory B cells (Bregs) and regulatory T cells (Tregs). Histological examination revealed marked pulmonary hemorrhage and structural injury shortly after CA. CA with CPR increased myeloid differentiation factor 88 (MyD88) mRNA and protein expression compared to controls at 2 h after CA. Cytokine analysis of BALF showed elevated IFN-γ, interleukin (IL)-1α, IL-1β, IL-2, IL-6, and IL-10 at 2 h after CA. A reduction in Bregs was noted at 2 h, whereas Tregs transiently increased between 2 and 4 h but declined at 6 h after CA. The MyD88-dependent signaling pathway appears to be rapidly activated in rats with CA after CPR, which may contribute to the early pulmonary inflammation observed as soon as 2 h after CA. Full article

This study successfully developed an oral vaccine for Type 1 Diabetes utilizing recombinant Lactococcus lactis expressing the GAD65 autoantigen. We conducted an in-depth investigation into its protective mechanisms in NOD mice, with a particular focus on its effects on the gut microbiota and metabolome. The administration of the GAD65-L. lactis vaccine resulted in a significant delay in diabetes onset and the preservation of pancreatic function. Our analyses revealed notable alterations in the gut microbial ecosystem, enhancing its diversity and the abundance of beneficial bacteria. Metabolomic profiling indicated time-dependent changes in metabolic pathways, with a marked enrichment of pyrimidine metabolism at 16 weeks and arachidonic acid metabolism at 24 weeks after vaccination by both GAD65-L. lactis and NZ9000-L. lactis. Integrated correlation analysis identified specific microbiota–metabolite interactions, including associations between Ruminiclostridium and lipid species in the GAD65-L. lactis group. These modifications in the microbial community and metabolic landscape were accompanied by enhanced immunoregulatory responses in intestinal LPLs, including expanded Treg populations and suppressed CD8⁺ T cells, a rising trend in IL-10-producing naive dendritic cells, and increased concentrations of TGF-β. Full article

This study aims to characterise the B cell compartment in a cohort of Sicilian centenarians by analysing absolute CD3⁻CD19⁺ lymphocyte counts, in association with age, sex, cytomegalovirus (CMV) serostatus, related to immune ageing, and interleukin (IL)-6 levels, representative of inflamm-ageing. It also investigates age-related changes in the CD4⁺/CD19⁺ ratio as a marker of immune ageing, reflecting shifts in immune homeostasis. B cell counts were assessed by flow cytometry on 53 Sicilians aged 19–110 years: 20 Adults, 15 Older adults, 11 long-living individuals, and 7 oldest centenarians. A multiple negative binomial regression was applied to evaluate the effects of age, sex, CMV serostatus, and Il-6 levels on values of B cells. The results showed a non-significant trend toward age-related decline without sex-based differences. A significant reduction in B cell count was observed in individuals with high anti_CMV titres, while IL-6 levels showed a borderline inverse correlation. CD4⁺/CD19⁺ ratio values showed an age-related increase. Our findings suggest that the age-related decline in B cell numbers may be mostly related to CMV infection and IL-6 values, without sex contribution. The age-related increase in the CD4⁺/CD19⁺ ratio, most pronounced in oldest centenarians, may represent a compensatory adaptation promoting immune regulation and chronic inflammation control. Full article

Chronic ulcerative colitis disrupts mucosal-acquired immunity; however, the relationship between mucosal regeneration and mucosa-associated lymph tissue (MALT) development remains unclear. We explored crypt responses, MALT phenotypes, and regulatory T cells (Tregs) in a mouse model of chronic colitis following two cycles of dextran sodium sulfate (DSS) exposure. The mucosal regeneration score correlated with crypt expression of Ki-67 and LGR5, submucosal FOXP3-positive Treg expression, and MALT scores. MALT can be categorized into solitary-isolated lymphoid structures, tertiary lymphoid structures, and colonic patches. Regenerative crypts adjacent to tertiary lymphoid structures exhibit reduced expression of Ki-67, LGR5, and SOX9, which might favor mucosal differentiation. These findings were further supported by correlations between crypt stem cell- and Treg-related colonic gene expression of Lgr5, Sox9, Wnt6, Ccl20, and IL10, and between Tgfb1 and Cxcl13. These results suggested that chronic colitis is repaired by stem cell-mediated mucosal regeneration and differentiation, potentially driven by the development of MALT-containing Tregs. Full article

The present review paper focuses on the peculiar environmental and health implications of fibrous amphibole “fluoro-edenite”, a new mineral first reported in Biancavilla (Etna Mount, Sicily, Italy). Its presence has been linked to an unusually high incidence of malignant pleural mesothelioma, as seen from national surveys during 1988–1997, marking the first case study of natural occurrence of fibrous amphibole in a volcanic context. Despite remediation efforts since the cessation of quarrying activities at the “Il Calvario” quarry, the risk of fiber exposure may extend beyond urban areas to surrounding soils and volcanic formation, not fully characterized yet. This review synthesizes relevant existing literature on mineralogical and chemical features of fluoro-edenite, while also enriching current understanding with new observations from optical microscopy, stereomicroscopy, and Scanning Electron Microscopy (SEM). Our analyses reveal the presence of fluoro-edenite amphibole not only in the altered samples but, significantly, within the massive rock samples. This finding expands its known distribution and offers initial consideration on public health implications related to massive lava rock, which crops out. This study highlights the importance of ongoing monitoring, detailed geological surveys, and further research into fiber occurrences and distribution in the volcanic systems, of which Mt. Etna represents the first case of natural occurrences, in order to fully assess their impact on public health. Full article

Inflammatory bowel disease (IBD) arises from chronic dysregulation at the epithelial–stromal interface, creating a need for in vitro systems that better capture these interactions. In this study, we developed a 3D co-culture platform in which HT-29 intestinal epithelial cells and IMR-90 fibroblasts are embedded within an alginate–gelatin hydrogel, alongside a complementary interface model using a plasma-treated electrospun mesh to spatially compartmentalize stromal and epithelial layers. We first assessed metabolic activity, viability, and proliferation across several epithelial-to-fibroblast ratios and identified 1:0.5 as the most supportive of epithelial expansion. The A1G7 hydrogel maintained high viability (>92%) and sustained growth in all mono- and co-cultures. To evaluate inflammatory competence, models were stimulated with lipopolysaccharide (LPS), administered either within the hydrogel or through the culture medium. LPS exposure increased TNF-α and IL-1β secretion in both configurations, with the magnitude of the response depending on the delivery route. Treatment with dexamethasone consistently reduced cytokine levels, confirming the model’s suitability for pharmacological testing. Together, these results demonstrate that the alginate–gelatin system provides a reproducible epithelial–stromal platform with quantifiable inflammatory readouts, offering a practical foundation for mechanistic studies and early-stage screening of anti-inflammatory therapeutics in IBD. Full article

Bone metastasis in breast cancer remains a major therapeutic challenge because current osteoclast-targeted therapies do not fully disrupt the tumor–bone vicious cycle. Osteocytes, the most abundant bone cells, are increasingly recognized as key regulators of bone–tumor crosstalk. Previous work has shown that osteocyte-specific overexpression of the Wnt co-receptor LRP5 inhibits breast cancer-induced osteolysis and generates conditioned medium (CM) with tumor-suppressive activity. Proteomic analysis identified LIM domain and actin-binding protein 1 (LIMA1) as a central mediator that interacts with Myosin Vb (MYO5B), suggesting the role of the LIMA1/MYO5B regulatory axis. This study demonstrates that CM derived from LRP5-overexpressing osteocytes suppresses EO771 breast cancer cell proliferation, migration, and invasion, and downregulates tumor-promoting proteins, including MMP9, Snail, IL-6, and TGF-β1, while upregulating the apoptosis-related protein cleaved caspase-3. These effects were largely reversed by knockdown of LIMA1 or MYO5B. In syngeneic mouse models of mammary tumors and bone metastasis, systemic administration of LRP5-overexpressing osteocyte-derived CM reduced tumor burden and osteolytic bone destruction, whereas genetic knockdown of LIMA1 in osteocytes or MYO5B in tumor cells abrogated these protective effects. Collectively, these findings indicate that LRP5 activation in osteocytes engages the LIMA1/MYO5B signaling axis that inhibits breast cancer progression and osteolysis, disrupts tumor–stromal interactions, and restores bone–tumor homeostasis, thereby providing a potential therapeutic strategy to break the vicious cycle of bone metastasis in breast cancer. Full article

Background: Psoriasis involving difficult-to-treat anatomical areas, such as the scalp, genitalia, fingernails, and palmoplantar regions, carries a disproportionate disease burden and often requires systemic therapy. In this context, real-life data comparing the long-term effectiveness of tildrakizumab 100 mg versus 200 mg in patients with difficult-to-treat psoriasis remain limited. Methods: This multicenter retrospective observational study included adult patients in three Italian dermatology centers. Global efficacy endpoints included PASI75, PASI90, PASI100, and absolute PASI ≤ 2 at weeks 16, 32, 52, and 104. Site-specific effectiveness was assessed as complete clearance (PGA = 0) in patients with baseline involvement (PGA ≥ 2) of difficult-to-treat areas. Outcomes were described by dose. Results: 183 patients were included (100 mg: n = 89; 200 mg: n = 94). Patients receiving 200 mg had higher baseline BMI and were more frequently biologic-experienced. At week 104, PASI75 was achieved by 94.2% of patients receiving 100 mg and 94.7% receiving 200 mg, while PASI90 and PASI100 were achieved by 82.7% vs. 57.9% and 48.1% vs. 47.4%, respectively. Clearance of difficult-to-treat areas improved progressively across all sites. Scalp and genital psoriasis showed higher and earlier clearance rates, whereas nail and palmoplantar psoriasis showed slower and more heterogeneous responses. No consistent dose-dependent advantage emerged, despite less favorable baseline characteristics in the 200 mg group. Conclusions: Over 104 weeks, tildrakizumab showed sustained long-term effectiveness in both global disease control and difficult-to-treat areas. The 200 mg dose, used in a more difficult-to-treat population, achieved comparable long-term outcomes, supporting dose optimization in clinical practice. Full article

Cosmeceutical peptides (CPs), which modulate various biological activities, including skin regeneration and wound healing, have emerged as promising agents in skincare. In this study, we investigated the regenerative and wound healing potential of a short peptide, CP-02 (sequence CDARSDAR), using human dermal fibroblast cells (HDFs) in vitro and a zebrafish model in vivo. In HDFs, CP-02 treatment at concentrations of 50, 100, and 200 µg/mL significantly accelerated wound closure in a dose-dependent manner (p < 0.05) and upregulated the mRNA expression of CCND1, MYC, FGF2, EFG, and IL-8 at 12 h post-treatment. In amputated zebrafish larvae, exposure to CP-02 (5 µg/mL) for 72 h significantly increased fin regeneration, with a fin area of 3.5 mm² and fin-fold length of 0.2 mm, compared with those in controls (2 mm² and 0.07 mm, respectively). Intramuscular administration of CP-02 significantly improved the healing rates in wounded adult zebrafish to 58% and 76% on 12 and 16 days post wounding (dpw), respectively, compared with the vehicle (35% and 44%, respectively). Histological analysis (H&E staining) revealed reduced inflammatory cell infiltration, complete granulation, and re-epithelialization in the CP-02-treated tissues at 12 dpw. Furthermore, mRNA expression levels of tnf-α, il-1β, tgfb1, mmp9, mmp13, and timp2b were elevated in the CP-02 group at 4 dpw, whereas those of pro-fibrotic mediators, including acta2, ctgfb, cdh1, and col9a3 reduced in muscle tissue on 12 dpw. Collectively these findings demonstrate that CP-02 promotes effective, scar-reducing regeneration and wound healing, highlighting its strong potential as a therapeutic peptide for future skincare and cosmeceutical applications. Full article

Investigation of the roots of Tripterygium wilfordii Hook. f. resulted in the isolation of nine sesquiterpene pyridine alkaloids (SPAs), including four previously undescribed compounds 1–4. The structures of all compounds were elucidated by extensive spectroscopic analysis, including NMR and HRESIMS. In particular, compound 1 was found to possess an unprecedented cage-like ether moiety, representing the first report of such a structural feature within this class of alkaloids. All isolated compounds were evaluated for their anti-inflammatory activity using a lipopolysaccharide (LPS)-induced RAW264.7 macrophage model. Compounds 1, 2, and 4 exhibited significant inhibition of nitric oxide (NO) production, with IC₅₀ values of 7.14 ± 1.89, 8.55 ± 0.37, and 14.76 ± 0.39 μM. Furthermore, compounds 1 and 2 suppressed the secretion of key pro-inflammatory cytokines, including TNF-α, IL-6, and IL-1β, in the same cellular model. These results not only enhanced the structural diversity of SPAs identified from T. wilfordii, but also highlight their potential as promising anti-inflammatory lead compounds. Full article

Connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH) is a severe form of pulmonary hypertension with poor prognosis. It most commonly arises in systemic sclerosis (SSc), followed by systemic lupus erythematosus (SLE) and mixed connective tissue disease (MCTD). Its pathogenesis involves a complex interplay of immune dysregulation, chronic inflammation, endothelial injury, vascular remodeling, and fibrosis. Although vasodilators targeting the endothelin, nitric oxide, and prostacyclin pathways remain the therapeutic backbone, newer agents—including the activin signal inhibitor sotatercept and inhaled treprostinil—have expanded treatment options. Immune-targeted therapies such as glucocorticoids, cyclophosphamide, mycophenolate mofetil, rituximab, and IL-6 receptor inhibitors may benefit inflammation-dominant PAH phenotypes, while fibrotic phenotypes continue to demonstrate limited responsiveness. In addition to brain natriuretic peptide (BNP), N-terminal (NT)-proBNP and disease-specific autoantibodies, emerging biomarkers show promise for early detection, risk stratification, and personalized treatment, though validation in CTD-PAH is lacking. Advances in animal models replicating immune-mediated vascular injury and fibrosis have further improved mechanistic understanding. Despite these developments, substantial unmet needs remain, including the absence of disease-specific therapeutic strategies, limited biomarker integration into clinical practice, and a scarcity of large, well-designed trials targeting individual CTD subtypes. Addressing these gaps will be essential for improving prognosis in patients with CTD-PAH. Full article