Role of the Receptor for Advanced Glycation End Products (RAGE) and Its Ligands in Inflammatory Responses.

Since its discovery in 1992, the receptor for advanced glycation end products (RAGE) has emerged as a key receptor in many pathological conditions, especially in inflammatory conditions. RAGE is expressed by most, if not all, immune cells and can be activated by many ligands. One characteristic of RAGE is that its ligands are structurally very diverse and belong to different classes of molecules, making RAGE a promiscuous receptor.

A computational model of the crosstalk between hepatocyte fatty acid metabolism and oxidative stress highlights the key enzymes, metabolites, and detoxification pathways in the context of MASLD.

Metabolic dysfunction-associated steatotic liver disease (MASLD; formerly known as NAFLD) is a common liver disease worldwide and carries the risk of progressing to severe liver conditions, such as fibrosis and liver cancer. In the context of MASLD, evaluating fat accumulation in the liver and the subsequent production of oxidative stress is essential to understand the disease propagation. However, clinical studies using human patients to investigate the fat accumulation and the onset of oxidative stress in MASLD face ethical and technical challenges, highlighting the importance of alternative methods.

Transcriptomic profiling analysis of the effect of palmitic acid on 3D spheroids of β-like cells derived from induced pluripotent stem cells.

Type 2 diabetes (T2D) is posing a serious public health concern with a considerable impact on human life and health expenditures worldwide. The disease develops when insulin plasma level is insufficient for coping insulin resistance, caused by the decline of pancreatic β-cell function and mass. In β-cells, the lipotoxicity exerted by saturated free fatty acids in particular palmitate (PA), which is chronically elevated in T2D, plays a major role in β-cell dysfunction and mass.

Dynamic, IPSC-derived hepatic tissue tri-culture system for the evaluation of liver physiology.

Availability of hepatic tissue for the investigation of metabolic processes is severely limited. While primary hepatocytes or animal models are widely used in pharmacological applications, a change in methodology towards more sustainable and ethical assays is highly desirable. Stem cell derived hepatic cells are generally regarded as a viable alternative for the above model systems, if current limitations in functionality and maturation can be overcome.

Screening for precancerous anal lesions linked to human papillomaviruses: French recommendations for clinical practice.

In France, about 2000 new cases of anal cancer are diagnosed annually. Squamous cell carcinoma is the most common histological type, mostly occurring secondary to persistent HPV16 infection. Invasive cancer is preceded by precancerous lesions.

Coculture model of a liver sinusoidal endothelial cell barrier and HepG2/C3a spheroids-on-chip in an advanced fluidic platform.

The liver is one of the main organs involved in the metabolism of xenobiotics and a key organ in toxicity studies. Prior to accessing the hepatocytes, xenobiotics pass through the hepatic sinusoid formed by liver sinusoidal endothelial cells (LSECs). The LSECs barrier regulates the kinetics and concentrations of the xenobiotics before their metabolic processing by the hepatocytes.

Correction: Generation of β-like cell subtypes from differentiated human induced pluripotent stem cells in 3D spheroids.

Correction for 'Generation of β-like cell subtypes from differentiated human induced pluripotent stem cells in 3D spheroids' by Lisa Morisseau , , 2023, https://doi.org/10.1039/d3mo00050h.

Generation of β-like cell subtypes from differentiated human induced pluripotent stem cells in 3D spheroids.

Since the identification of four different pancreatic β-cell subtypes and bi-hormomal cells playing a role in the diabetes pathogenesis, the search for models that mimics such cells heterogeneity became a key priority in experimental and clinical diabetology. We investigated the potential of human induced pluripotent stem cells to lead to the development of the different β-cells subtypes in honeycomb microwell-based 3D spheroids. The glucose-stimulated insulin secretion confirmed the spheroids functionality.

The Gigli saw, a useful tool for cutting a metal ring causing penile strangulation.

Penile strangulation is a rare pediatric urology emergency. A 13-year-old boy with no psychiatric history was referred to the university hospital 2 h after a metallic ring was self-placed over his penis. Under general anesthesia, a Gigli saw cut the cockring in two places.

S100s and HMGB1 Crosstalk in Pancreatic Cancer Tumors.

Pancreatic cancer remains a disease that is very difficult to treat. S100 proteins are small calcium binding proteins with diverse intra- and extracellular functions that modulate different aspects of tumorigenesis, including tumor growth and metastasis. High mobility group box 1 (HMGB1) protein is a multifaceted protein that also actively influences the development and progression of tumors.

Development of a lung-liver in vitro coculture model for inhalation-like toxicity assessment.

Animal models are considered prime study models for inhalation-like toxicity assessment. However, in light of animal experimentation reduction (3Rs), we developed and investigated an alternative in vitro method to study systemic-like responses to inhalation-like exposures. A coculture platform was established to emulate inter-organ crosstalks between a pulmonary barrier, which constitutes the route of entry of inhaled compounds, and the liver, which plays a major role in xenobiotic metabolism.

Investigation of the metabolomic crosstalk between liver sinusoidal endothelial cells and hepatocytes exposed to paracetamol using organ-on-chip technology.

Organ-on-chip technology is a promising in vitro approach recapitulating human physiology for the study of responses to drug exposure. Organ-on-chip cell cultures have paved new grounds for testing and understanding metabolic dose-responses when evaluating pharmaceutical and environmental toxicity. Here, we present a metabolomic investigation of a coculture of liver sinusoidal endothelial cells (LSECs, SK-HEP-1) with hepatocytes (HepG2/C3a) using advanced organ-on-chip technology.

Transcriptomic and proteomic studies suggest the establishment of advanced zonation-like profiles in human-induced pluripotent stem cell-derived liver sinusoidal endothelial cells and carboxypeptidase M-positive liver progenitor cells cocultured in a fluidic microenvironment.

Aim: Hepatic zonation is a physiological feature of the liver, known to be key in the regulation of the metabolism of nutrients and xenobiotics and the biotransformation of numerous substances. However, the reproduction of this phenomenon remains challenging in vitro as only part of the processes involved in the orchestration and maintenance of zonation are fully understood. The recent advances in organ-on-chip technologies, which allow for the integration of multicellular 3D tissues in a dynamic microenvironment, could offer solutions for the reproduction of zonation within a single culture vessel.

Catalyst-Free Thia-Michael Addition to α-Trifluoromethylacrylates for 3D Network Synthesis.

Thia-Michael additions (1,4-additions of a thiol to a Michael acceptor) are generally catalyzed by an external Brønsted or Lewis base. A spontaneous (uncatalyzed) Michael addition of thiols to α-trifluoromethyl acrylates is described, as well as its application to the very efficient preparation of a thermoset. A thorough mechanistic investigation, based on an experimental kinetic study and on DFT calculations, is presented for the addition of arene- and alkanethiols to tert-butyl trifluoromethyl acrylate in polar aprotic solvents, unveiling a probable solvent-assisted proton transfer in the rate-determining step and a considerable lowering of the energy barrier induced by the CF group.

Investigation of the Exometabolomic Profiles of Rat Islets of Langerhans Cultured in Microfluidic Biochip.

Diabetes mellitus (DM) is a complex disease with high prevalence of comorbidity and mortality. DM is predicted to reach more than 700 million people by 2045. In recent years, several advanced in vitro models and analytical tools were developed to investigate the pancreatic tissue response to pathological situations and identify therapeutic solutions.

Real-world comparison of effectiveness between tofacitinib and vedolizumab in patients with ulcerative colitis exposed to at least one anti-TNF agent.

Background: Data comparing tofacitinib and vedolizumab in ulcerative colitis (UC) are lacking.

Aims: To compare the effectiveness of tofacitinib and vedolizumab in patients with UC who had prior exposure to anti-TNF therapy METHODS: In this multicentre study, we included consecutive patients with UC ≥18 years old with partial Mayo score >2 and prior anti-TNF exposure, who started tofacitinib or vedolizumab between January 2019 and June 2021. Comparisons were performed using propensity score analyses (inverse probability of treatment weighting).

A novel agonist for the HGF receptor MET promotes differentiation of human pluripotent stem cells into hepatocyte-like cells.

Hepatocyte growth factor (HGF) is the natural ligand of the MET receptor tyrosine kinase. This ligand-receptor couple is essential for the maturation process of hepatocytes. Previously, the rational design of a synthetic protein based on the assembly of two K1 domains from HGF led to the production of a potent and stable MET receptor agonist.

Development of Liver-on-Chip Integrating a Hydroscaffold Mimicking the Liver's Extracellular Matrix.

The 3Rs guidelines recommend replacing animal testing with alternative models. One of the solutions proposed is organ-on-chip technology in which liver-on-chip is one of the most promising alternatives for drug screening and toxicological assays. The main challenge is to achieve the relevant in vivo-like functionalities of the liver tissue in an optimized cellular microenvironment.