Investigating the delivery of PD-L1-targeted immunoliposomes in a dynamic cervical cancer-on-a-chip model.

The recent approval of pembrolizumab in recurrent or metastatic cervical cancer warrants further investigations into the usefulness of immunotherapies for more durable and less radical interventions. In this study, the targeting potential of anti-PD-L1-functionalized immunoliposomes was tested in a 3D in vitro cervical cancer-on-a-chip model. Immunolipsomes were synthesized and decorated externally with monovalent anti-PD-L1 Fab' fragments of commercially available atezolizumab.

Large, recursive membrane platforms are associated to Trop-1, Trop-2 and protein kinase signaling for cell growth.

The transmembrane glycoproteins Trop-1/EpCAM and Trop-2 independently trigger Ca and kinase signals for cell growth and tumor progression. Our findings indicated that Trop-1 and Trop-2 tightly colocalize at macroscopic, ruffle-like protrusions (RLP), that elevate from the cell perimeter, and locally recur over hundreds of seconds. These previously unrecognized elevated membrane regions ≥20 µm-long, up to 1.

Human enteric glia diversity in health and disease: new avenues for the treatment of Hirschsprung disease.

Background And Aims: The enteric nervous system (ENS), comprised of neurons and glia, regulates intestinal motility. Hirschsprung disease (HSCR) results from defects in ENS formation, yet while neuronal aspects have been extensively studied, enteric glia remain disregarded. This study aimed to explore enteric glia diversity in health and disease.

Non-stem cell lineages as an alternative origin of intestinal tumorigenesis in the context of inflammation.

According to conventional views, colon cancer originates from stem cells. However, inflammation, a key risk factor for colon cancer, has been shown to suppress intestinal stemness. Here, we used Paneth cells as a model to assess the capacity of differentiated lineages to trigger tumorigenesis in the context of inflammation in mice.

Defect healing and doping of CVD graphene by thermal sulfurization.

CVD graphene layers are intrinsically polycrystalline; depending on grain size, their structure at the atomic level is scarcely free of defects, which affects the properties of graphene. On the one hand, atomic-scale defects act as scattering centers and lead to a loss of carrier mobility. On the other hand, structural disorder at grain boundaries provides additional resistance in series that affects material conductivity.

Tropomyosin1 isoforms underlie epithelial to mesenchymal plasticity, metastatic dissemination, and resistance to chemotherapy in high-grade serous ovarian cancer.

Phenotypic plasticity, defined as the ability of individual cells with stable genotypes to exert different phenotypes upon exposure to specific environmental cues, represent the quintessential hallmark of the cancer cell en route from the primary lesion to distant organ sites where metastatic colonization will occur. Phenotypic plasticity is driven by a broad spectrum of epigenetic mechanisms that allow for the reversibility of epithelial-to-mesenchymal and mesenchymal-to-epithelial transitions (EMT/MET). By taking advantage of the co-existence of epithelial and quasi-mesenchymal cells within immortalized cancer cell lines, we have analyzed the role of EMT-related gene isoforms in the regulation of epithelial mesenchymal plasticity (EMP) in high grade serous ovarian cancer.

On the role of polymeric hydrogels in the thermal response of gold nanorods under NIR laser irradiation.

Hydrogels are 3D cross-linked networks of polymeric chains designed to be used in the human body. Nowadays they find widespread applications in the biomedical field and are particularly attractive as drug delivery vectors. However, despite many good results, their release performance is sometimes very quick and uncontrolled, being forced by the high clearance of body fluids.

Turn-Mimic Hydantoin-Based Loops Constructed by a Sequential Multicomponent Reaction.

A collection of peptidomimetics characterized by having an aspartic acid motif embedded in a rigid hydantoin heterocycle are synthesized through a sequential multicomponent domino process followed by standard regioselective deprotection/coupling reactions based on acid-base liquid/liquid purification protocols. H nuclear magnetic resonance experiments, molecular modeling, and X-ray analysis showed that the resulting hydantoin-based loops I (in particular) and II (to a lesser extent) can be considered novel β-turn inducer motifs being able to project two peptide-like strands in a U-shaped conformation driven by the formation of intermolecular hydrogen bonds.

The origin of intestinal cancer in the context of inflammation.

According to conventional views, colon cancer originates from stem cells. However, inflammation, a key risk factor for colon cancer, was shown to suppress intestinal stemness. Here, we employed Paneth cells (PCs) as a model to assess the capacity of differentiated lineages to trigger tumorigenesis in the context of inflammation.

Synthesis and Characterization of New Triazole-Bispidinone Scaffolds and Their Metal Complexes for Catalytic Applications.

Bispidines are a family of ligands that plays a pivotal role in various areas of coordination chemistry, with applications in medicinal chemistry, molecular catalysis, coordination polymers synthesis, and molecular magnetism. In the present work, triazole moieties were introduced using the CuAAC click-reaction, with the aim of expanding the number of coordination sites on the bispidine core. The 1,2,3-triazole rings were thus synthesized on propargyl-derived bispidines after reaction with different alkyl azides.

β-Cyclodextrin functionalized agarose-based hydrogels for multiple controlled drug delivery of ibuprofen.

Agarose hydrogels are three-dimensional hydrophilic polymeric frameworks characterised by high water content, viscoelastic properties, and excellent ability as cell and drug delivery systems. However, their hydrophilicity as gel systems makes loading of hydrophobic drugs difficult and often ineffective. The incorporation of amphiphilic molecules (e.

Emergency Department Arrival Modes: Time for Mandatory Pediatric Readiness.

Introduction: Because small children can be transported by private vehicles, many children seek emergency care outside of Emergency Medical Services (EMS). Such transports may access the closest emergency departments (EDs) without knowledge of their pediatric competence. This study quantifies this practice and the concept of mandatory pediatric readiness.

Evidence-based management of pulmonary embolism in the emergency department.

Patients with pulmonary emboli present both diagnostic and therapeutic challenges to the emergency clinician, because initial symptoms can be variable and overlap with other medical conditions. This issue reviews treatment options for patients with pulmonary emboli based on risk stratification scores of low, intermediate-low, intermediate-high, and high risk classifications. The evidence on laboratory testing and imaging is presented, as well as treatment strategies that include anticoagulation, thrombolytics, and mechanical or surgical thrombectomy.

3D-Informed Targeting of the Trop-2 Signal-Activation Site Drives Selective Cancer Vulnerability.

Next-generation Trop-2-targeted therapy against advanced cancers is hampered by expression of Trop-2 in normal tissues. We discovered that Trop-2 undergoes proteolytic activation by ADAM10 in cancer cells, leading to the exposure of a previously inaccessible protein groove flanked by two N-glycosylation sites. We designed a recognition strategy for this region, to drive selective cancer vulnerability in patients.

A combinatorial panel for flow cytometry-based isolation of enteric nervous system cells from human intestine.

Efficient isolation of neurons and glia from the human enteric nervous system (ENS) is challenging because of their rare and fragile nature. Here, we describe a staining panel to enrich ENS cells from the human intestine by fluorescence-activated cell sorting (FACS). We find that CD56/CD90/CD24 co-expression labels ENS cells with higher specificity and resolution than previous methods.

Paneth cells as the origin of intestinal cancer in the context of inflammation.

Paneth cells (PCs), responsible for the secretion of antimicrobial peptides in the small intestine and for niche support to crypt-base columnar stem cells (CBCs), have been shown to respond to inflammation by dedifferentiating into stem-like cells in order to sustain a regenerative response. Therefore, PCs may represent the cells-of-origin of intestinal cancer in the context of inflammation. To test this hypothesis, we targeted and mutations in Paneth cells by Cre-Lox technology and modelled inflammation by dextran sodium sulfate (DSS) administration.

Pd-Loaded Cellulose NanoSponge as a Heterogeneous Catalyst for Suzuki-Miyaura Coupling Reactions.

The (eco)design and synthesis of durable heterogeneous catalysts starting from renewable sources derived from biomass waste represents an important step for reducing environmental impacts of organic transformations. Herein, we report the efficient loading of Pd(II) ions on an eco-safe cellulose-based organic support (CNS), obtained by thermal cross-linking between TEMPO-oxidized cellulose nanofibers and branched polyethyleneimine in the presence of citric acid. A 22.

Recycling of used vegetable oils by powder adsorption.

The treatment of used vegetable oil (UVO) with seven different adsorbents and through two different procedures (stirring and gravity filtration) was explored. Important differences in terms of density, turbidity, electrical resistance, free fatty acids (FFAs) content and relative fatty acid distribution were observed. Different outcomes were shown depending both on the adsorbent and on the procedure.

Alternative splicing downstream of EMT enhances phenotypic plasticity and malignant behavior in colon cancer.

Phenotypic plasticity allows carcinoma cells to transiently acquire the quasi-mesenchymal features necessary to detach from the primary mass and proceed along the invasion-metastasis cascade. A broad spectrum of epigenetic mechanisms is likely to cause the epithelial-to-mesenchymal (EMT) and mesenchymal-to-epithelial (MET) transitions necessary to allow local dissemination and distant metastasis. Here, we report on the role played by alternative splicing (AS) in eliciting phenotypic plasticity in epithelial malignancies with focus on colon cancer.

Synthesis and Conformational Analysis of Hydantoin-Based Universal Peptidomimetics.

The synthesis of a collection of enantiomerically pure, systematically substituted hydantoins as structural privileged universal mimetic scaffolds is presented. It relies on a chemoselective condensation/cyclization domino process between isocyanates of quaternary or unsubstituted α-amino esters and -alkyl aspartic acid diesters followed by standard hydrolysis/coupling reactions with amines, using liquid-liquid acid/base extraction protocols for the purification of the intermediates. Besides the nature of the α carbon on the isocyanate moiety, either a quaternary carbon or a more flexible methylene group, conformational studies (molecular modeling), in solution (NMR, circular dichroism (CD), Fourier transform infrared (FTIR)), and in solid state (X-ray) showed that the presented hydantoin-based peptidomimetics are able to project their substituents in positions superimposable to the side chains of common protein secondary structures such as α-helix and β-turn, being the open α-helix conformation slightly favorable according to molecular modeling, while the closed β-turn conformation preferred in solution and in solid state.

Effective hole conductivity in nitrogen-doped CVD-graphene by singlet oxygen treatment under photoactivation conditions.

Nitrogen substitutional doping in the π-basal plane of graphene has been used to modulate the material properties and in particular the transition from hole to electron conduction, thus enlarging the field of potential applications. Depending on the doping procedure, nitrogen moieties mainly include graphitic-N, combined with pyrrolic-N and pyridinic-N. However, pyridine and pyrrole configurations of nitrogen are predominantly introduced in monolayer graphene:N lattice as prepared by CVD.