Search Results (50)

Polymethyl methacrylate nanoparticles functionalized with three different compounds, acrylic acid (AA), curcumin (CUR), and fumaramide (FA), were tested in a two-step solid–liquid extraction process (extraction and stripping) for yttrium recovery. In both stages, the best conditions were determined: pH, solid–liquid ratio and the compound with the highest affinity for yttrium recovery, obtaining 90% of efficiency for both stages in a single work cycle. The results obtained by SEM ruled out the growing of nanoparticles by swelling and confirmed the formation of structural arrangements by the addition of the metal to the system. In addition, there is evidence that the recovery process can be selective considering the mixing of rare earth elements through changes in pH. Using isothermal titration calorimetry (ITC), the thermodynamic properties of the extraction process were calculated, understanding the system as the union of a macromolecule and a ligand. The results showed that the extraction process was spontaneous and highly entropic. Full article

In celiac disease (CeD), interleukin 15 (IL-15) affects the epithelial barrier by acting on intraepithelial lymphocytes, promoting interferon γ (IFN-γ) production and inducing strong cytotoxic activity as well as eliciting apoptotic death of enterocytes by the Fas/Fas ligand system. This study investigates the effects of a monoclonal antibody neutralizing the effects of IL-15 (aIL-15) on tissue-damaging immune response in untreated CeD patients by using an organ culture system. Jejunal biopsies from 10 untreated CeD patients were cultured ex vivo with or without aIL-15. Epithelial expressions of CD95/Fas, HLA-E and perforin were analyzed by immunohistochemistry. Apoptosis was detected in the epithelium by using the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. Additionally, the surface epithelium compartment of ex vivo cultured biopsy samples was isolated by laser capture microdissection (LCM). RNA from each LCM sample was extracted and the relative expression of IFN-γ was evaluated by quantitative reverse transcriptase-PCR (qRT-PCR). Biopsies cultured with the aIL-15 antibody showed a reduction in Fas, HLA-E and perforin epithelial expression, as well as a decrease in epithelial TUNEL+ cells compared to biopsies cultured without the aIL-15 antibody. Moreover, downregulation of epithelial IFN-γ expression was recorded in biopsies incubated with aIL-15, compared to those cultured without aIL-15. Our findings suggest that neutralizing the effects of IL-15 in ex vivo cultured untreated CeD intestinal mucosa could block apoptosis by downregulating Fas and HLA-E expression and the release of cytotoxic proteins, such as perforin. Furthermore, it can dampen the hyperactive immune response by reducing IFN-γ expression. More generally, our study provides new evidence for the effects of anti-IL-15 neutralizing monoclonal antibodies in preventing or repairing epithelial damage and further supports the concept that IL-15 is a meaningful therapeutic target in CeD, or inflammatory diseases associated with the upregulation of IL-15. Full article

Two Fe-based hybrids, [SiO₂@NP(Ph)₂/Fe^II/PP₃] and [SiO₂@NP(t-Bu)₂/Fe^II/PP₃], were synthesized using the double-ligand approach by covalently grafting NP ligands onto the surface of SiO₂. Both catalytic systems were evaluated for H₂ production through formic acid dehydrogenation (FADH), revealing important efficiency without requiring additional additives and/or co-catalysts. During the continuous addition of FA, [SiO₂@NP(Ph)₂/Fe^II/PP₃] and [SiO₂@NP(t-Bu)₂/Fe^II/PP₃] demonstrated great stability, achieving total TONs = 20,636 and 20,854, respectively. FT-IR and Raman spectroscopy provided insights into the role of NP ligands, such as NP(Ph)₂ and NP(t-Bu)₂, on the assembly and structural configuration of active hybrid Fe catalysts and their ability to dehydrogenate formic acid. Additional studies, including in situ mapping of the solution potential (E_h) of the catalytic reaction and an Arrhenius study of the activation energy (E_a), revealed a correlation between E_a and H₂ production rates: the system [SiO₂@NP(Ph)₂/Fe^II/PP₃] with an E_a = 29.4 KJ/mol shows an H₂ production rate of 58 mL-H₂/min, while [SiO₂@NP(t-Bu)₂/Fe^II/PP₃] with a E_a = 50.6 KJ/mol shows an H₂ production rate of 55 mL-H₂/min. This is the first example of a heterogeneous FADH system where the original strategy of a “double-ligand” has been demonstrated for homogeneous FADH catalytic systems. Herein we demonstrate that we can engineer a decrease in the activation barrier Ea via two synergistic steps: (i) via grafting of the NP ligand onto SiO₂ and (ii) using PP₃ as double ligand. This strategy leads to a boost in the H₂ production efficiency of [SiO₂@NP(Ph)₂/Fe^II/PP₃] as a heterogeneous catalyst, which for the first time has been shown to be able to outperform the parental reference/homogenous catalyst [Fe^II/PP₃]. Full article

The Fas/Fas ligand (FasL) system is a major apoptosis-regulating pathway with a key role in tumor immune surveillance and metastasis. The expression of Fas/FasL on mammary tumor tissues holds prognostic value for breast cancer (BC) patients. We herein assessed Fas/FasL expression on circulating tumor cells (CTCs) and matched peripheral blood mononuclear cells (PBMCs) from 98 patients with metastatic BC receiving first-line treatment. Fas+, FasL+, and Fas+/FasL+ CTCs were identified in 88.5%, 92.3%, and 84.6% of CTC-positive patients, respectively. In addition, Fas+/FasL+, Fas-/FasL+, and Fas-/FasL- PBMCs were identified in 70.3%, 24.2%, and 5.5% of patients, respectively. A reduced progression-free survival (PFS) was revealed among CTC-positive patients (median PFS: 9.5 versus 13.4 months; p = 0.004), and specifically among those harboring Fas+/FasL+ CTCs (median PFS: 9.5 vs. 13.4 months; p = 0.009). On the other hand, an increased overall survival (OS) was demonstrated among patients with Fas+/FasL+ PBMCs rather than those with Fas-/FasL+ and Fas-/FasL- PBMCs (median OS: 35.7 vs. 25.9 vs. 14.4 months, respectively; p = 0.008). These data provide for the first time evidence on Fas/FasL expression on CTCs and PBMCs with significant prognostic value for patients with metastatic BC, thus highlighting the role of the Fas/FasL system in the peripheral immune response and metastatic progression of BC. Full article

Metabolic dysfunction-associated steatotic liver disease/steatohepatitis (MASLD/MASH) is a major disease worldwide whose effective treatment is challenging. Peroxisome proliferator-activated receptors (PPARs) belong to the nuclear receptor superfamily and function as ligand-activated transcription factors. To date, three distinct subtypes of PPARs have been characterized: PPARα, PPARβ/δ, and PPARγ. PPARα and PPARγ are crucial regulators of lipid metabolism that modulate the transcription of genes involved in fatty acid (FA), bile acid, and cholesterol metabolism. Many PPAR agonists, including natural (FAs, eicosanoids, and phospholipids) and synthetic (fibrate, thiazolidinedione, glitazar, and elafibranor) agonists, have been developed. Furthermore, recent advancements in nanoparticles (NPs) have led to the development of new strategies for MASLD/MASH therapy. This review discusses the applications of specific cell-targeted NPs and highlights the potential of PPARα- and PPARγ-targeted NP drug delivery systems for MASLD/MASH treatment. Full article

Two types of iron-based catalysts, [Fe/SiO₂@^iProPNP/PP3] and [Fe/SiO₂@^tBuPNP/PP3], for the dehydrogenation of formic acid (FADH), were synthesized. These catalysts were developed using a double-ligand approach combining a PNP ligand and a PP3 ligand, demonstrating functionality without the need for additional cocatalysts or additives. Furthermore, hybrid catalysts [Fe/SiO₂@^iProPNP/PP3] and [Fe/SiO₂@^tBuPNP/PP3] were created by covalently grafting PNP ligands onto SiO₂ particles. The hybrid [Fe/SiO₂@^iProPNP/PP3] exhibited enhanced recyclability, with turnover numbers (TONs) exceeding 74,000. In situ ATR-FTIR and UV-Vis spectroscopies were used to monitor the structure and dynamics of the catalysts under catalytic conditions, revealing the formation of active catalysts through the involvement of all components: [Fe (metal)/PNP (first ligand)/PP3 (second ligand)/FA (substrate)], which are crucial to FADH catalysis. An Arrhenius study revealed that the hybrid [Fe/SiO₂@^iProPNP/PP3] had a lower activation energy (E_a = 42.5 kJ/mol) compared to its homogeneous counterpart (E_a = 48.2 kJ/mol), indicating superior catalytic performance. Conversely, [Fe/SiO₂@^tBuPNP/PP3] showed an increased activation energy (E_a = 48.3 kJ/mol) compared to its homogeneous form (E_a = 46.4 kJ/mol). This study discusses the differing roles of ^tBuPNP and ^iProPNP in catalyst configuration, highlighting the potential of double-ligand catalysts to enhance the performance and recyclability of PNP ligands in FADH, offering significant implications for the development of efficient and reusable catalytic systems. Full article

The current focus of ovarian cancer (OC) research is the improvement of treatment options through maximising drug effectiveness. OC remains the fifth leading cause of cancer-induced mortality in women worldwide. In recent years, nanotechnology has revolutionised drug delivery systems. Nanoparticles may be utilised as carriers in gene therapy or to overcome the problem of drug resistance in tumours by limiting the number of free drugs in circulation and thereby minimising undesired adverse effects. Cell surface receptors, such as human epidermal growth factor 2 (HER2), folic acid (FA) receptors, CD44 (also referred to as homing cell adhesion molecule, HCAM), and vascular endothelial growth factor (VEGF) are highly expressed in ovarian cancer cells. Generation of active targeting nanoparticles involves modification with ligands that recognise cell surface receptors and thereby promote internalisation by cancer cells. Several poly(ADP-ribose) polymerase (PARP) inhibitors (PARPi) are currently used for the treatment of high-grade serous ovarian carcinomas (HGSOC) or platinum-sensitive relapsed OC. However, PARP resistance and poor drug bioavailability are common challenges, highlighting the urgent need to develop novel, effective strategies for ovarian cancer treatment. This review evaluates the utility of nanoparticles in ovarian cancer therapy, with a specific focus on targeted approaches and the use of PARPi nanocarriers to optimise treatment outcomes. Full article

The use of targeted drug delivery systems, including those based on selective absorption by certain receptors on the surface of the target cell, can lead to a decrease in the minimum effective dose and the accompanying toxicity of the drug, as well as an increase in therapeutic efficacy. A fullerene C₆₀ conjugate (FA-PVP-C₆₀) with polyvinylpyrrolidone (PVP) as a biocompatible spacer and folic acid (FA) as a targeting ligand for tumor cells with increased expression of folate receptors (FR) was obtained. Using ¹³C NMR spectroscopy, FT-IR, UV-Vis spectrometry, fluorometry and thermal analysis, the formation of the conjugate was confirmed and the nature of the binding of its components was established. The average particle sizes of the conjugate in aqueous solutions and cell culture medium were determined using dynamic light scattering (DLS) and nanoparticle tracking analysis (NTA). The FA-PVP-C₆₀ showed antiradical activity against ^•DPPH, ^•OH and O₂^•−, but at the same time, it was shown to generate ¹O₂. It was found that the conjugate in the studied concentration range (up to 200 μg/mL) is non-toxic in vitro and does not affect the cell cycle. To confirm the ability of the conjugate to selectively accumulate through folate-mediated endocytosis, its uptake into cells was analyzed by flow cytometry and confocal microscopy. It was shown that the conjugate is less absorbed by A549 cells with low FR expression than by HeLa, which has a high level of expression of this receptor. Full article

Kidney transplantation offers a longer life expectancy and a better quality of life than dialysis to patients with end-stage kidney disease. Ischemia–reperfusion injury (IRI) is thought to be a cornerstone in delayed or reduced graft function and increases the risk of rejection by triggering the immunogenicity of the organ. IRI is an unavoidable event that happens when the blood supply is temporarily reduced and then restored to an organ. IRI is the result of several biological pathways, such as transcriptional reprogramming, apoptosis and necrosis, innate and adaptive immune responses, and endothelial dysfunction. Tubular cells mostly depend on fatty acid (FA) β-oxidation for energy production since more ATP molecules are yielded per substrate molecule than glucose oxidation. Upon ischemia–reperfusion damage, the innate and adaptive immune system activates to achieve tissue clearance and repair. Several cells, cytokines, enzymes, receptors, and ligands are known to take part in these events. The complement cascade might start even before organ procurement in deceased donors. However, additional experimental and clinical data are required to better understand the pathogenic events that take place during this complex process. Full article

Ischemic stroke-induced neuronal cell death leads to the permanent impairment of brain function. The Fas-mediating extrinsic apoptosis pathway and the cytochrome c-mediating intrinsic apoptosis pathway are two major molecular mechanisms contributing to neuronal injury in ischemic stroke. In this study, we employed a Fas-blocking peptide (FBP) coupled with a positively charged nona-arginine peptide (9R) to form a complex with negatively charged siRNA targeting Bax (FBP9R/siBax). This complex is specifically designed to deliver siRNA to Fas-expressing ischemic brain cells. This complex enables the targeted inhibition of Fas-mediating extrinsic apoptosis pathways and cytochrome c-mediating intrinsic apoptosis pathways. Specifically, the FBP targets the Fas/Fas ligand signaling, while siBax targets Bax involved in mitochondria disruption in the intrinsic pathway. The FBP9R carrier system enables the delivery of functional siRNA to hypoxic cells expressing the Fas receptor on their surface—a finding validated through qPCR and confocal microscopy analyses. Through intranasal (IN) administration of FBP9R/siCy5 to middle cerebral artery occlusion (MCAO) ischemic rat models, brain imaging revealed the complex specifically localized to the Fas-expressing infarcted region but did not localize in the non-infarcted region of the brain. A single IN administration of FBP9R/siBax demonstrated a significant reduction in neuronal cell death by effectively inhibiting Fas signaling and preventing the release of cytochrome c. The targeted delivery of FBP9R/siBax represents a promising alternative strategy for the treatment of brain ischemia. Full article

Light-responsive liposomes have been developed for the on-demand release of drugs. However, efficient delivery of chemotherapeutic drugs to tumor for cancer theranostics remains a challenge. Herein, folic acid (FA), an established ligand for targeted drug delivery, was used to decorate light-sensitive porphyrin-phospholipid (PoP) liposomes, which were assessed for FA-targeted chemophototherapy (CPT). PoP liposomes and FA-conjugated PoP liposomes were loaded with Doxorubicin (Dox), and physical properties were characterized. In vitro, FA-PoP liposomes that were incubated with FA receptor-overexpressing human KB cancer cells showed increased uptake compared to non-targeted PoP liposomes. Dox and PoP contributed towards chemophototherapy (CPT) in vitro, and PoP and FA-PoP liposomes induced cell killing. In vivo, mice bearing subcutaneous KB tumors treated with PoP or FA-PoP liposomes loaded with Dox, followed by 665 nm laser treatment, had delayed tumor growth and improved survival. Dox delivery to tumors increased following laser irradiation for both PoP and FA-PoP liposomes. Thus, while Dox-FA-PoP liposomes were effective following systemic administration and local light irradiation in this tumor model, the FA targeting moiety did not appear essential for anti-tumor responses. Full article

Although experimental models have shown that the innate immune system is a main contributor to acute kidney injury (AKI), its involvement in human sepsis-associated AKI (SA-AKI) remains unclear. We retrospectively evaluated 19 patients with SA-AKI who were treated with continuous renal replacement therapy (CRRT). Serum cytokine, complement components, and the proportion and functions of innate immune cells, such as CD56⁺ T cells, CD56⁺ natural killer (NK) cells, and monocytes, were analyzed. There were no differences in the proportions of CD56⁺ T and NK cells between patients with SA-AKI and healthy controls. In patients with SA-AKI, fas ligand (FasL) expression in CD56⁺ T cells was significantly upregulated, and the proportion of perforin-positive CD56⁺ T cells tended to be higher than that in healthy controls. The positive rate of both FasL and perforin of CD56⁺ T cells was significantly higher than that of CD56^- T cells, which include cytotoxic T cells. Antigen-presenting capacity and phagocytic activity of monocytes in patients with SA-AKI were significantly decreased compared to those of healthy controls and did not recover soon after the initiation of CRRT. CD56⁺ T cells are involved in the disease processes of human SA-AKI through effector molecules such as FasL or perforin. Full article

Three imidazole-based hybrid materials, coded as IGOPS, IPS and impyridine@SiO₂ nanohybrids, were prepared via the covalent immobilization of N-ligands onto a mesoporous nano-SiO₂ matrix for H₂ generation from formic acid (FA). BET and HRTEM demonstrated that the immobilization of the imidazole derivative onto SiO₂ has a significant effect on the SSA, average pore volume, and particle size distribution. In the context of FA dehydrogenation, their catalytic activity (TONs, TOFs), stability, and reusability were assessed. Additionally, the homologous homogeneous counterparts were evaluated for comparison purposes. Mapping the redox potential of solution E_h vs. SHE revealed that poly-phosphine PP₃ plays an essential role in FA dehydrogenation. On the basis of performance and stability, [Fe²⁺/IGOPS/PP₃] demonstrated superior activity compared to other heterogeneous catalysts, producing 9.82 L of gases (VH₂ + CO₂) with TONs = 31,778, albeit with low recyclability. In contrast, [Fe²⁺/IPS/PP₃] showed the highest stability, retaining considerable performance after three consecutive uses. With VH₂ + CO₂ = 7.8 L, [Fe²⁺/impyridine@SiO₂/PP₃] activity decreased, and it was no longer recyclable. However, the homogeneous equivalent of [Fe²⁺/impyridine/PP₃] was completely inactive. Raman, FT/IR, and UV/Vis spectroscopy demonstrated that the reduced recyclability of [Fe²⁺/IGOPS/PP₃] and [Fe²⁺/impyridine@SiO₂/PP₃] nanohybrids is due to the reductive cleavage of their C-O-C bonds during catalysis. An alternative grafting procedure is proposed, applying here to the grafting of IPS, resulting in its higher stability. The accumulation of water derived from substrate’s feeding causes the inhibition of catalysis. In the case of [Fe²⁺-imidazole@SiO₂] nanohybrids, simple washing and drying result in their re-activation, overcoming the water inhibition. Thus, the low-cost imidazole-based nanohybrids IGOPS and IPS are capable of forming [Fe²⁺/IGOPS/PP₃] and [Fe²⁺/IPS/PP₃] heterogeneous catalytic systems with high stability and performance for FA dehydrogenation. Full article

MicroRNA 193a-3p (miR193a-3p) is a short non-coding RNA with tumor suppressor properties. Breast cancer (BC) progression is governed by active interaction between breast cancer cells, vascular (V)/lymphatic (L) endothelial cells (ECs), and BC secretome. We have recently shown that miR193a-3p, a tumor suppressor miRNA, inhibits MCF-7 BC cell-driven growth of VECs via direct antimitogenic actions and alters MCF-7 secretome. Since LEC-BC cross-talk plays a key role in BC progression, we investigated the effects of miR193a-3p on MCF-7 secretome and estradiol-mediated growth effects in LECs and LEC + MCF-7 spheroids, and delineated the underlying mechanisms. Transfection of LECs with miR193a-3p, as well as secretome from MCF-7 transfected cells, inhibited LEC growth, and these effects were mimicked in LEC + MCF-7 spheroids. Moreover, miR193a-3p inhibited ERK1/2 and Akt phosphorylation in LECs and LEC + MCF-7 spheroids, which are importantly involved in promoting cancer development and metastasis. Treatment of LECs and LEC + MCF-7 spheroids with estradiol (E2)-induced growth, as well as ERK1/2 and Akt phosphorylation, and was abrogated by miR193a-3p and secretome from MCF-7 transfected cells. Gene expression analysis (GEA) in LEC + MCF-7 spheroids transfected with miR193a-3p showed significant upregulation of 54 genes and downregulation of 73 genes. Pathway enrichment analysis of regulated genes showed significant modulation of several pathways, including interferon, interleukin/cytokine-mediated signaling, innate immune system, ERK1/2 cascade, apoptosis, and estrogen receptor signaling. Transcriptomic analysis showed downregulation in interferon and anti-apoptotic and pro-growth molecules, such as IFI6, IFIT1, OSA1/2, IFITM1, HLA-A/B, PSMB8/9, and PARP9, which are known to regulate BC progression. The cytokine proteome array of miR193a-3p transfected MCF secretome and confirmed the upregulation of several growth inhibitory cytokines, including IFNγ, Il-1a, IL-1ra, IL-32, IL-33, IL-24, IL-27, cystatin, C-reactive protein, Fas ligand, MIG, and sTIM3. Moreover, miR193a-3p alters factors in MCF-7 secretome, which represses ERK1/2 and Akt phosphorylation, induces pro-apoptotic protein and apoptosis in LECs, and downregulates interferon-associated proteins known to promote cancer growth and metastasis. In conclusion, miR193a-3p can potentially modify the tumor microenvironment by altering pro-growth BC secretome and inhibiting LEC growth, and may represent a therapeutic molecule to target breast tumors/cancer. Full article

To overcome the severe side effects of cancer chemotherapy, it is vital to develop targeting chemotherapeutic delivery systems with the potent inhibition of tumour growth, angiogenesis, invasion and migration at low drug dosages. For this purpose, we co-loaded a conventional antiworm drug, albendazole (ABZ), and a TOPK inhibitor, OTS964, into lipid-coated calcium phosphate (LCP) nanoparticles for skin cancer treatment. OTS- and ABZ-loaded LCP (OTS-ABZ-LCP) showed a synergistic cytotoxicity against skin cancer cells through their specific cancerous pathways, without obvious toxicity to healthy cell lines. Moreover, dual-targeting the programmed death ligand-1 (PD-L1) and folate receptor overexpressed on the surface of skin cancer cells completely suppressed the skin tumour growth at low doses of ABZ and OTS. In summary, ABZ and OTS co-loaded dual-targeting LCP NPs represent a promising platform with high potentials against complicated cancers where PD-L1/FA dual targeting appears as an effective approach for efficient and selective cancer therapy. Full article