Gold Nanoparticle Detection with Two-Photon Excitation Fluorescence Lifetime Imaging of NAD(P)H in Cancer Cells: An Analytical Approach to Separate Nanoparticle and NAD(P)H Signals.

Gold nanoparticles (AuNPs) have shown promise for applications in the diagnosis and treatment of different diseases, including cancer. Understanding the effect of AuNPs on metabolic reprogramming in cancer cells at the single cell level is of high importance for improving the efficacy and safety. Fluorescence lifetime imaging microscopy (FLIM) of nicotinamide adenine dinucleotide (phosphate) hydrogen (NAD(P)H) as a main metabolic cofactor and an indicator of metabolic reprogramming in cancer cells enables real-time monitoring of cancer cell metabolism in response to different treatments, including AuNPs.

Promoting the Efficacy of Deferiprone-Gallium-Protoporphyrin (IX) against Intracellular Infection with Lipid Liquid Crystalline Nanoparticles.

Nontuberculous mycobacteria (NTM) are among the recalcitrant bacterial strains that cause difficult-to-treat infections for patients with chronic underlying pulmonary conditions. The bacteria's intrinsic resistance to various antibiotics and their ability to infect macrophages enable them to overcome both the host immune response and standard antibiotics. Unconventional approaches to treating NTM-mediated infections are required.

Enhancing non-viral DNA delivery systems: Recent advances in improving efficiency and target specificity.

DNA-based therapies are often limited by challenges such as stability, long-term integration, low transfection efficiency, and insufficient targeted DNA delivery. This review focuses on recent progress in the design of non-viral delivery systems for enhancing targeted DNA delivery and modulation of therapeutic efficiency. Cellular uptake and intracellular trafficking mechanisms play a crucial role in optimizing gene delivery efficiency.

phage therapy candidates from Sphae: An automated toolkit for predicting sequencing data.

Motivation: Phage therapy is a viable alternative for treating bacterial infections amidst the escalating threat of antimicrobial resistance. However, the therapeutic success of phage therapy depends on selecting safe and effective phage candidates. While experimental methods focus on isolating phages and determining their lifecycle and host range, comprehensive genomic screening is critical to identify markers that indicate potential risks, such as toxins, antimicrobial resistance, or temperate lifecycle traits.

Alternate Sampling Matrices for Therapeutic Drug Monitoring of Immunosuppressants.

Background: Immunosuppressant (IS) therapeutic drug monitoring (TDM) relies on measuring mostly pharmacologically inactive erythrocyte-bound and/or plasma protein-bound drug levels. Variations in hematocrit and plasma protein levels complicate interpretation of blood calcineurin inhibitor (CNI) and inhibitors of the molecular target of rapamycin (mTORi) concentrations. Variable binding of mycophenolic acid (MPA) to albumin similarly complicates its TDM in plasma.

Nonlinear biomechanical behaviour of extracranial carotid artery aneurysms in the framework of Windkessel effect via FSI technique.

Extracranial carotid artery aneurysms (ECCA) lead to rupture and neurologic symptoms from embolisation, with potentially fatal outcomes. Investigating the biomechanical behaviour of EECA with blood flow dynamics is crucial for identifying regions more susceptible to rupture. A coupled three-dimensional (3D) Windkessel-framework and hyperelastic fluid-structure interaction (FSI) analysis of ECCAs with patient-specific geometries, was developed in this paper with a particular focus on hemodynamic parameters and the arterial wall's biomechanical response.

Association of health status and hospitalization risk for peripheral artery disease in the PORTRAIT registry.

Background: Healthcare utilization for patients with peripheral artery disease (PAD) is high, but stratifying patients' risk of hospitalization at initial evaluation is challenging. We examined the association between health status at PAD presentation and risk of (1) combined all-cause hospital admissions and emergency department (ED) visits and (2) all-cause hospital admissions.

Methods: Patients with claudication enrolled at US sites in the PORTRAIT registry were included.

Randomised Placebo-Controlled Pilot Trial Evaluating the Anti-Anginal Efficacy of Ticagrelor in Patients with Angina with Nonobstructive Coronary Arteries and Coronary Slow Flow Phenomenon.

: The coronary slow flow phenomenon (CSFP) is an angiographic finding characterised by the delayed passage of contrast through the coronary arteries, despite the absence of obstructive coronary artery disease (defined as less than 50% narrowing of the vessel lumen). Patients with the CSFP experience recurrent angina, for which there are limited evidence-based therapies. Ticagrelor may serve as an effective anti-anginal therapy for these patients by increasing adenosine levels, which could alleviate coronary microvascular dysfunction and its associated angina due to its vasodilatory properties.

Characterising the role of enolase in a stable Small Colony Variant of Staphylococcus aureus isolated from a diabetic foot infection patient with osteomyelitis.

The switch to alternate cell types by Staphylococcus aureus creates sub-populations even within an active population, that are highly resilient, tolerant to antibiotics and lack clinical symptoms of infection. These cells present a challenge for clinical treatment where even after initial intervention has seemingly cleared the infection, these alternate cell types persist within tissue to revert and cause disease. Small colony variants (SCV) are a cell type which facilitate persistent infection but clinically isolated SCVs are often unstable in laboratory conditions.

Fludrocortisone dose-response relationship in septic shock: a randomised phase II trial.

Background: The combination of intravenous hydrocortisone and enteral fludrocortisone may reduce mortality in patients with septic shock. The optimal dose and reliability of absorption of fludrocortisone in critically ill patients are unclear.

Methods: In a multi-centre, open label, phase II randomized clinical trial, intravenous hydrocortisone alone or in combination with one of three doses of enteral fludrocortisone (50 µg, 100 µg or 200 µg daily) for 7 days was compared in patients with septic shock.

Osteomyelitis-relevant antibiotics at clinical concentrations show limited effectivity against acute and chronic intracellular infections in osteocytes.

Osteomyelitis caused by can involve the persistent infection of osteocytes. We sought to determine if current clinically utilized antibiotics were capable of clearing an intracellular osteocyte infection. Rifampicin, vancomycin, levofloxacin, ofloxacin, amoxicillin, oxacillin, doxycycline, linezolid, gentamicin, and tigecycline were assessed for their minimum inhibitory concentration (MIC) and minimum bactericidal concentrations against 12 strains, at pH 5.

Solving genomic puzzles: computational methods for metagenomic binning.

Metagenomics involves the study of genetic material obtained directly from communities of microorganisms living in natural environments. The field of metagenomics has provided valuable insights into the structure, diversity and ecology of microbial communities. Once an environmental sample is sequenced and processed, metagenomic binning clusters the sequences into bins representing different taxonomic groups such as species, genera, or higher levels.

Clinical toxicology of acute glyphosate self-poisoning: impact of plasma concentrations of glyphosate, its metabolite and polyethoxylated tallow amine surfactants on the toxicity.

Introduction: Common major co-formulants in glyphosate-based herbicides, polyethoxylated tallow amine surfactants, are suspected of being more toxic than glyphosate, contributing to the toxicity in humans. However, limited information exists on using polyethoxylated tallow amine concentrations to predict clinical outcomes. We investigated if plasma concentrations of glyphosate, its metabolite and polyethoxylated tallow amines can predict acute kidney injury and case fatality in glyphosate poisoning.

Deferiprone and Gallium-Protoporphyrin Chitogel as an antimicrobial treatment: Preclinical studies demonstrating antimicrobial activity for S. aureus infected cutaneous wounds.

Staphylococcus aureus (S. aureus) is one of the most common wound pathogens with increased resistance towards currently available antimicrobials. S.

Enhanced RHO-ROCK signaling is associated with CRELD2 production and fibroblast recruitment in cutaneous squamous cell carcinoma.

A key characteristic of cancer cells is their ability to induce changes in their microenvironment that render it permissive to tumor growth, invasion and metastasis. Indeed, these changes are required for tumor progression. Consequently, the tumor microenvironment is emerging as a key source of new targets against cancer, with novel therapies aimed at reversing tumor-promoting changes, reinstating a tumor-hostile microenvironment and suppressing disease progression.

Temporally resolved proteomics identifies nidogen-2 as a cotarget in pancreatic cancer that modulates fibrosis and therapy response.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by increasing fibrosis, which can enhance tumor progression and spread. Here, we undertook an unbiased temporal assessment of the matrisome of the highly metastatic KPC (, , ) and poorly metastatic KPC (, , ) genetically engineered mouse models of pancreatic cancer using mass spectrometry proteomics. Our assessment at early-, mid-, and late-stage disease reveals an increased abundance of nidogen-2 (NID2) in the KPC model compared to KPC, with further validation showing that NID2 is primarily expressed by cancer-associated fibroblasts (CAFs).