Tubulin detyrosination shapes cytoskeletal architecture and virulence.

Tubulin detyrosination has been implicated in various human disorders and is important for regulating microtubule dynamics. While in most organisms this modification is restricted to α-tubulin, in trypanosomatid parasites, it occurs on both α- and β-tubulin. Here, we show that in , a single vasohibin (LmVASH) enzyme is responsible for differential kinetics of α- and β-tubulin detyrosination.

The F508del-CFTR trafficking correctors elexacaftor and tezacaftor are CFTR-independent Ca-mobilizing agonists normalizing abnormal Ca levels in human airway epithelial cells.

Background: Cystic fibrosis (CF) is caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) channel. For people with CF (pwCF) affected by the most common pathogenic variant F508del, a tritherapy, named Trikafta/Kaftrio (ETI: elexacaftor (VX-445) /tezacaftor (VX-661) / ivacaftor (VX-770)) was successfully developed. However, in CF airway epithelial cells the calcium homeostasis is also disturbed; it is observed an increased calcium mobilization in CF cells compared to non-CF cells.

New Plant Extracts Exert Complementary Anti-Hair Loss Properties in Human In Vitro and Ex Vivo Models.

Background: Hair loss is linked to dysfunction of the growth (anagen), regression (catagen) and rest (telogen) phases of the hair follicle (HF) cycle.

Aims: To evaluate the effects of a Silybum marianum extract (SME), manganese PCA (MnPCA), and a Lespedeza capitata extract (LCE) on markers of hair growth and anchorage in human follicle dermal papilla cells (HFDPCs), and to investigate the ability of a topical serum containing these active ingredients to improve HF growth in an ex vivo human scalp skin model.

Methods: In HFDPCs, we assessed receptor tyrosine kinase phosphorylation and Wnt/β-catenin pathway activation; quantified versican, vascular endothelial growth factor (VEGF) and Dickkopf-1 (DDK1) secretion; and evaluated 5α-reductase (5αR) activity.

Dental pulp mesenchymal stem cells-response to fibrin hydrogel reveals ITGA2 and MMPs expression.

Regenerative endodontic procedures (REP) aim at reestablishing tooth vitality by replacing the irreversibly damaged dental pulp removed by the dental practitioner with a new functional one. The current treatment of advanced caries relies on the replacement of the inflamed or necrosed dental pulp with an inert filling material. This leads to a functional but non-vital tooth, which lacks the ability to sense dental tissue damage, and to protect from further bacterial attack.

Bioactive Endodontic Hydrogels: From Parameters to Personalized Medicine.

Regenerative endodontic procedures (REPs) aim at recreating dental pulp tissue using biomaterials such as hydrogels. Their bioactivity is mostly related to the nature of biomolecules or chemical compounds that compose the endodontic hydrogel. However, many other parameters, such as hydrogel concentration, bioactive molecules solubility, and apex size, were reported to influence the reciprocal host-biomaterial relationship and hydrogel behavior.

Next generation antibacterial strategies for regenerative endodontic procedures: A scoping review.

Background: The clinical results following regenerative endodontic procedures (REPs) vary according to numerous parameters, including the presence of bacteria. This limitation reduces the indications for REPs and calls for the development of next generation antibacterial strategies (NGAS) providing alternatives to current antibacterial strategies (CAS) such as double or triple antibiotic paste (DAP/TAP) and (Ca(OH)2).

Objectives: The present scoping review aims to describe the current trends regarding the use of such strategies and highlight future perspectives.

Refractory Bronchopulmonary Infection After Lung Transplantation for Common Variable Immunodeficiency Despite Maximal Treatment Including IgM/IgA-Enriched Immunoglobulins and Bacteriophage Therapy.

Recipients transplanted for bronchiectasis in the context of a primary immune deficiency, such as common variable immunodeficiency, are at a high risk of severe infection in post-transplantation leading to poorer long-term outcomes than other transplant indications. In this report, we present a fatal case due to chronic bronchopulmonary infection in a lung transplant recipient with common variable immunodeficiency despite successful eradication of an extensively drug-resistant (XDR) strain with IgM/IgA-enriched immunoglobulins and bacteriophage therapy. The fatal evolution despite a drastic adaptation of the immunosuppressive regimen and the maximal antibiotic therapy strategy raises the question of the contraindication of lung transplantation in such a context of primary immunodeficiency.

[Supply of sterile medical devices to an interventional technical platform via mobile RFID technology].

This work presents the eight-month assessment of the mobile RFID (radio frequency identification) technology implementation for the management of sterile medical devices in an interventional cardiology department. Several indicators dedicated to stock management, organizational impact (within the pharmacy and the department) and economic impact were collected. The scope of MDS tracked by RFID was defined as well as the new supply circuit.

A Polymer Prodrug Strategy to Switch from Intravenous to Subcutaneous Cancer Therapy for Irritant/Vesicant Drugs.

Chemotherapy is almost exclusively administered via the intravenous (IV) route, which has serious limitations (e.g., patient discomfort, long hospital stays, need for trained staff, high cost, catheter failures, infections).

Microplastics: What happens in the human digestive tract? First evidences in adults using in vitro gut models.

Microplastics (MPs) are ubiquitous in the environment and humans are inevitably exposed to them. However, the effects of MPs in the human digestive environment are largely unknown. The aim of our study was to investigate the impact of repeated exposure to polyethylene (PE) MPs on the human gut microbiota and intestinal barrier using, under adult conditions, the Mucosal Artificial Colon (M-ARCOL) model, coupled with a co-culture of intestinal epithelial and mucus-secreting cells.

Aqueous synthesis and self-assembly of bioactive and thermo-responsive HA--ELP bioconjugates.

The design of synthetic (bio)macromolecules that combine biocompatibility, self-assembly and bioactivity properties at the molecular level is an intense field of research for biomedical applications such as (nano)medicine. In this contribution, we have designed and synthesized a library of bioactive and thermo-responsive bioconjugates from elastin-like polypeptides (ELPs) and hyaluronic acid (HA) in order to access bioactive self-assembled nanoparticles. These were prepared by a simple synthetic and purification strategy, compatible with the requirements for biological applications and industrial scale-up.

Maternal heme-enriched diet promotes a gut pro-oxidative status associated with microbiota alteration, gut leakiness and glucose intolerance in mice offspring.

Maternal environment, including nutrition and microbiota, plays a critical role in determining offspring's risk of chronic diseases such as diabetes later in life. Heme iron requirement is amplified during pregnancy and lactation, while excessive dietary heme iron intake, compared to non-heme iron, has shown to trigger acute oxidative stress in the gut resulting from reactive aldehyde formation in conjunction with microbiota reshape. Given the immaturity of the antioxidant defense system in early life, we investigated the extent to which a maternal diet enriched with heme iron may have a lasting impact on gut homeostasis and glucose metabolism in 60-day-old C3H/HeN mice offspring.

Diagnosis of Congenital Toxoplasmosis: No Benefit of IgA Antibody Detection by Platelia ELISA in a Tricentric Evaluation.

The diagnostic accuracy of a commercial Toxoplasma gondii IgA antibody enzyme-linked immunosorbent assay (ELISA) was evaluated in the context of routine practice on 289 newborns with congenital toxoplasmosis (CT) and 220 healthy controls. The performance of this assay was compared to that of the current gold-standard test for anti- IgM detection, an immunosorbent agglutination assay (ISAGA). IgM and IgA sensitivity and specificity were assessed in cord and postnatal samples.

Diagnosis of Congenital Toxoplasmosis: Performance of Four IgG and IgM Automated Assays at Birth in a Tricentric Evaluation.

For postnatal diagnosis of congenital toxoplasmosis (CT), the gold standard for the detection of anti- IgM in newborns relies on the immunosorbent agglutination assay (ISAGA), which is manufactured from whole parasites that become difficult to maintain. For IgG, only the Platelia assay provides a validated assay for cord blood according to the manufacturer, allowing its use in this context. We compared the analytical performance of four commercialized automated assays, Platelia, Abbott, Vidas, and Liaison, for the detection of IgG and IgM in the cord blood or peripheral blood of newborns from women infected during pregnancy.

The challenge of diagnosing Guillain-Barre syndrome in patients with COVID-19 in the intensive care unit.

Various neurological complications have been described in COVID-19 patients, especially Guillain-Barre syndrome (GBS). The underlying mechanisms on the association between SARS-CoV-2 infection and GBS remain unclear, but several hypotheses have been proposed. It seems that post-SARS-CoV-2 GBS shares many characteristics with classic post-infectious GBS; however, it may occur in sedated and intubated patients hospitalized in the intensive care unit for SARS-CoV-2 acute respiratory distress syndrome, which presents challenges in the diagnosis and treatment of GBS.

The rescue of F508del-CFTR by elexacaftor/tezacaftor/ivacaftor (Trikafta) in human airway epithelial cells is underestimated due to the presence of ivacaftor.

Trikafta, currently the leading therapeutic in cystic fibrosis (CF), has demonstrated a real clinical benefit. This treatment is the triple combination therapy of two folding correctors elexacaftor/tezacaftor (VX445/VX661) plus the gating potentiator ivacaftor (VX770). In this study, our aim was to compare the properties of F508del-CFTR in cells treated with either lumacaftor (VX809), tezacaftor, elexacaftor, elexacaftor/tezacaftor with or without ivacaftor.

Photooxidation Responsive Elastin-Like Polypeptide Conjugates for Photodynamic Therapy Application.

Stimuli-responsive recombinant elastin-like polypeptides (ELPs) are artificial protein polymers derived from the hydrophobic domain of tropoelastin that have attracted significant interest for drug delivery and tissue engineering applications. In the present study, we have conjugated a photosensitizer (PS) to a hydrophobic methionine-containing ELP scaffold, which upon reaction with singlet oxygen (O) is transformed into a hydrophilic sulfoxide derivative facilitating the disassembly of photosensitizer-delivery particles during the photodynamic therapy (PDT) process. A peripherally substituted carboxy-Zn(II)-phthalocyanine derivative (TT1) bearing a carboxyl group directly linked to the Pc-ring, and presenting an absorption maximum around 680 nm, was selected as PS which simultaneously acted as a photooxidation catalyst.

Multicenter Comparative Assessment of the TIB MolBiol Toxoplasma gondii Detection Kit and Four Laboratory-Developed PCR Assays for Molecular Diagnosis of Toxoplasmosis.

Toxoplasmosis can be a life-threatening infection, particularly during pregnancy and in immunocompromised patients. The biological diagnosis of toxoplasmosis is challenging and has been revolutionized by molecular detection methods. This article summarizes the data of a multicenter study involving four centers to assess the performances of a commercial PCR assay as compared with four in-house PCR assays using Toxoplasma gondii standards, 20 external quality control specimens, and 133 clinical samples.

Repeated exposure of Caco-2 versus Caco-2/HT29-MTX intestinal cell models to (nano)silver in vitro: Comparison of two commercially available colloidal silver products.

Colloidal silver products are sold for a wide range of disinfectant and health applications. This has increased the potential for human exposure to silver nanoparticles (AgNPs) and ions (Ag), for which oral ingestion is considered to be a major route of exposure. Our objective was to evaluate and compare the toxicity of two commercially available colloidal silver products on two human intestinal epithelial models under realistic exposure conditions.

Gene Editing in Trypanosomatids: Tips and Tricks in the CRISPR-Cas9 Era.

Gene editing in trypanosomatids has long been proven difficult. The development of CRISPR-Cas9 has improved this issue, opening the way to a better understanding of biological processes and drug-resistance mechanisms, and screening of drug targets. Different strategies have now been developed: either PCR- or plasmid-based, differing mainly in the nature of the donor DNA and the single guide RNA transcription.

Fine Tuning of Calcium Constitutive Entry by Optogenetically-Controlled Membrane Polarization: Impact on Cell Migration.

Anomalies in constitutive calcium entry (CCE) have been commonly attributed to cell dysfunction in pathological conditions such as cancer. Calcium influxes of this type rely on channels, such as transient receptor potential (TRP) channels, to be constitutively opened and strongly depend on membrane potential and a calcium driving force. We developed an optogenetic approach based on the expression of the halorhodopsin chloride pump to study CCE in non-excitable cells.

Rapid diagnostic tests failing to detect infections by Plasmodium falciparum encoding pfhrp2 and pfhrp3 genes in a non-endemic setting.

Background: Rapid diagnostic tests (RDTs) detecting the histidine-rich protein 2 (PfHRP2) have a central position for the management of Plasmodium falciparum infections. Yet, variable detection of certain targeted motifs, low parasitaemia, but also deletion of pfhrp2 gene or its homologue pfhrp3, may result in false-negative RDT leading to misdiagnosis and delayed treatment. This study aimed at investigating the prevalence, and understanding the possible causes, of P.