Targeted delivery of napabucasin with radiotherapy improves outcomes in diffuse midline glioma.

Background: Diffuse midline glioma (DMG) is the most aggressive primary brain tumor in children. All previous studies examining the role of systemic agents have failed to demonstrate a survival benefit; the only standard of care is radiation therapy (RT). Successful implementation of radiosensitization strategies in DMG remains an essential and promising avenue of investigation.

Elucidation and Pharmacologic Targeting of Master Regulator Dependencies in Coexisting Diffuse Midline Glioma Subpopulations.

Diffuse Midline Gliomas (DMGs) are universally fatal, primarily pediatric malignancies affecting the midline structures of the central nervous system. Despite decades of clinical trials, treatment remains limited to palliative radiation therapy. A major challenge is the coexistence of molecularly distinct malignant cell states with potentially orthogonal drug sensitivities.

Coated Cotton Fabrics with Antibacterial and Anti-Inflammatory Silica Nanoparticles for Improving Wound Healing.

Herein, we report the preparation of bifunctional silica nanoparticles by covalent attachment of both an anti-inflammatory drug (ibuprofen) and an antibiotic (levofloxacin or norfloxacin) through amide groups. We also describe the coating of cotton fabrics with silica nanoparticles containing both ibuprofen and norfloxacin moieties linked by amide groups by using a one-step coating procedure under ultrasonic conditions. The functionalized nanoparticles and cotton fabrics have been characterized using spectroscopic and microscopic techniques.

Systematic elucidation and pharmacological targeting of tumor-infiltrating regulatory T cell master regulators.

Due to their immunosuppressive role, tumor-infiltrating regulatory T cells (TI-Tregs) represent attractive immuno-oncology targets. Analysis of TI vs. peripheral Tregs (P-Tregs) from 36 patients, across four malignancies, identified 17 candidate master regulators (MRs) as mechanistic determinants of TI-Treg transcriptional state.

Bronchoscopy in Critically Ill COVID-19 Patients: Findings, Microbiological Profile, and Coinfection.

Background: Bronchoscopy is a widely use technique in critically ill patients. Nosocomial coinfections are a cause of morbidity and mortality in intensive care units.

Objectives: Our aim was to describe bronchoscopy findings and analyze microbiological profile and probably coinfection through bronchial aspirate (BA) samples in patients with coronavirus disease 2019 pneumonia requiring intensive care unit admission.

Epithelial TLR4 Signaling Activates DUOX2 to Induce Microbiota-Driven Tumorigenesis.

Background & Aims: Chronic colonic inflammation leads to dysplasia and cancer in patients with inflammatory bowel disease. We have described the critical role of innate immune signaling via Toll-like receptor 4 (TLR4) in the pathogenesis of dysplasia and cancer. In the current study, we interrogate the intersection of TLR4 signaling, epithelial redox activity, and the microbiota in colitis-associated neoplasia.

Release of functional fibroblast growth factor-2 from artificial inclusion bodies.

Growth factors are required for cell proliferation and differentiation under physiological conditions but especially in the context of regenerative medicine. The time-prolonged administration of those factors has been explored using different sustained drug delivery systems. These platforms include natural materials such as bacterial inclusion bodies (IBs) that contain chaperones and other bacterial components that might favour protein release.

Anti-inflammatory Cotton Fabrics and Silica Nanoparticles with Potential Topical Medical Applications.

The preparation of functional cotton fabrics and silica nanoparticles by direct covalent linking of nonsteroidal anti-inflammatory drugs (salicylic acid, ibuprofen, and diclofenac) through an amide group is reported. Moreover, the coating of cotton fabrics with silica nanoparticles functionalized with such antiinflamatory agents is found to increase the roughness of the surface, providing hydrophobicity to the modified fabrics. This property is enhanced by the addition of fluorinated alkyl silane in the co-condensation process to form the coating solution.

Fluid supplementation accelerates epithelial repair during chemical colitis.

The dextran sulfate sodium (DSS) model of colitis is a common animal model of inflammatory bowel disease that causes pain and distress. In this study, we aimed to determine whether fluid supplementation can be used as a welfare-based intervention to minimize animal suffering. C57Bl/6 females undergoing acute colitis by administration of 3% DSS in drinking water were supplemented with 1 mL intraperitoneal injections of NaCl and compared to non-supplemented control mice.

Loss of Impairs Hedgehog-Driven Medulloblastoma Tumorigenesis.

The AMP-activated protein kinase (AMPK) is a sensor of cellular energy status that has a dual role in cancer, i.e., pro- or anti-tumorigenic, depending on the context.

TLR2 and TLR9 modulate enteric nervous system inflammatory responses to lipopolysaccharide.

Background: Accumulating evidence suggest that the enteric nervous system (ENS) plays important roles in gastrointestinal inflammatory responses, which could be in part mediated by Toll-like receptor (TLR) activation. The aim of this study was to characterise the expression and functionality of TLR2/4/9 in the ENS.

Methods: TLR2/4/9 expression was assessed in the plexuses of adult rats and embryonic ENS cultures by immunofluorescence and quantitative PCR.

Craniosynostosis, psychomotor retardation, and facial dysmorphic features in a Spanish patient with a 4q27q28.3 deletion.

Case Report: We describe an unusual clinical case with an 11-Mb deletion at 4q27 (chr4: 123094652-134164491), craniosynostosis (CS), mild psychomotor retardation, and facial dysmorphic features. This deletion involves 18 genes; FGF2, NUDT6, and SPRY1 are primarily or secondarily implicated in human cranial bone and sagittal suture development and could play an important role in CS.

Conclusions: Clinicians should always contemplate genetic studies in patients with syndromic CS.

Cerebral palsy, epilepsy, and severe intellectual disability in a patient with 3q29 microduplication syndrome.

Interstitial microduplication of 3q29 has been recently described. Individuals with this syndrome have widely variable phenotypes. We describe the first clinical case with a 1.

Short-fiber protein of ad40 confers enteric tropism and protection against acidic gastrointestinal conditions.

The lack of vectors for selective gene delivery to the intestine has hampered the development of gene therapy strategies for intestinal diseases. We hypothesized that chimeric adenoviruses of Ad5 (species C) displaying proteins of the naturally enteric Ad40 (species F) might hold the intestinal tropism of the species F and thus be useful for gene delivery to the intestine. As oral-fecal dissemination of enteric adenovirus must withstand the conditions encountered in the gastrointestinal tract, we studied the resistance of chimeric Ad5 carrying the short-fiber protein of Ad40 to acid milieu and proteases and found that the Ad40 short fiber confers resistance to inactivation in acidic conditions and that AdF/40S was further activated upon exposure to low pH.

Functional inclusion bodies produced in bacteria as naturally occurring nanopills for advanced cell therapies.

Inclusion bodies (50-500 nm in diameter) produced in recombinant bacteria can be engineered to contain functional proteins with therapeutic potential. Upon exposure, these protein particles are efficiently internalized by mammalian cells and promote recovery from diverse stresses. Being fully biocompatible, inclusion bodies are a novel platform, as tailored nanopills, for sustained drug release in advanced cell therapies.

Functionally enhanced siRNA targeting TNFα attenuates DSS-induced colitis and TLR-mediated immunostimulation in mice.

Tumor necrosis factor (TNFα) is a proinflammatory cytokine involved in the pathogenesis of inflammatory bowel disease (IBD). Although TNFα has been extensively targeted using systemic drugs, the use of antisense and small interfering RNA (siRNA) to drive down its expression at the site of inflammation should provide important advantages. In this study, native and chemically modified siRNA against TNFα was developed and characterized using a murine model of IBD.

TORAFIC study protocol: torasemide prolonged release versus furosemide in patients with chronic heart failure.

Unlabelled: Loop diuretics, such as torasemide and furosemide, are important agents in the treatment of chronic heart failure. Beneficial effects of torasemide immediate-release formulation beyond diuresis have been documented as the ability of this compound to inhibit myocardial synthesis and deposition of collagen type I in patients with chronic heart failure. In addition, torasemide-treated patients, but not furosemide-treated patients, showed decreased serum concentrations of the C-terminal propeptide of procollagen type I, a biochemical marker of myocardial fibrosis.

Neuromuscular changes in a rat model of colitis.

Intracolonic administration of Trichinella spiralis larvae in rats causes colitis with features similar to ulcerative colitis, notably with inflammation predominantly limited to the colonic mucosa. Our aim was to characterize the functional and neurochemical changes occurring within the myenteric (MP) and submucosal plexuses (SMP) during T. spiralis-induced colitis.

Time course of neural and contractile disturbances in a rat model of colitis induced by Trichinella spiralis.

Colitis induced by Trichinella spiralis in rat induces alterations in the spontaneous motor pattern displayed by circular colonic muscle [Auli, M., Fernandez, E., 2005.

Role of enteric glia in intestinal physiology: effects of the gliotoxin fluorocitrate on motor and secretory function.

The role of enteric glia in gastrointestinal physiology remains largely unexplored. We examined the actions of the gliotoxin fluorocitrate (FC) on intestinal motility, secretion, and inflammation after assessing its efficacy and specificity in vitro. FC (100 microM) caused a significant decrease in the phosphorylation of the glucose analog 2-[N-(7-nitrobenz-2-oxa-1,3-diaz-4-yl)amino]-2-deoxyglucose in enteric glial cultures and a reduction in glial uptake of the fluorescent dipeptide Ala-Lys-7-amino-4-methylcoumarin-3-acetic acid in both the ileum and colon.

Alterations in intestinal contractility during inflammation are caused by both smooth muscle damage and specific receptor-mediated mechanisms.

Aim: To evaluate motoric intestinal disturbances during inflammation with Trichinella spiralis in rats as an experimental model.

Methods: We examined the changes in worm-positive (jejunum) and worm-free (ileum) intestinal segments of rats infected with T. spiralis.

Characterization of functional and morphological changes in a rat model of colitis induced by Trichinella spiralis.

We intended to characterize the effect of inflammation on the spontaneous colonic motility pattern and the role of iNOS in its disruption in colitis. Colitis was induced by an intracolonic enema of T. spiralis larvae.

Changes in the inhibitory responses to electrical field stimulation of intestinal smooth muscle from Trichinella spiralis infected rats.

Functional motor changes and morphological alterations have been associated with intestinal inflammation. The aim of this work was to study functional motor changes in inflamed and non-inflamed intestinal segments of Trichinella spiralis infected rats. Thickness of muscle layers and cell infiltration during infection were also evaluated.

A spindle checkpoint arrest and a cytokinesis failure by the dominant-negative polo-box domain of Plk1 in U-2 OS cells.

Polo kinases play critical roles for proper M-phase progression. They are characterized by the presence of two regions of homology in the C-terminal non-catalytic domain, termed polo-box 1 (PB1) and polo-box 2 (PB2). Here we demonstrate that both PB1 and PB2 are required for targeting the catalytic activity of Plk1 to centrosomes, midbody, and kinetochores.