Effects and risk assessment of halogenated bisphenol A derivatives on human follicle stimulating hormone receptor: An interdisciplinary study.

Halogenated bisphenol A (BPA) derivatives are produced during disinfection treatment of drinking water or are synthesized as flame retardants (TCBPA or TBBPA). BPA is considered as an endocrine disruptor especially on human follicle-stimulating hormone receptor (FSHR). Using a global experimental approach, we assessed the effect of halogenated BPA derivatives on FSHR activity and estimated the risk of halogenated BPA derivatives to the reproductive health of exposed populations.

Fatty Liver Disease Along Cushing Syndrome Evolution.

Context: The clinical manifestations of Cushing syndrome are variable, but an important number of patients present a metabolic syndrome, strongly associated with hepatic steatosis.

Objective: The aim of this study was to determine the prevalence of metabolic dysfunction associated steatotic liver disease (MASLD) at the diagnosis of Cushing syndrome.

Methods: We conducted a single-center retrospective study at Angers Hospital (France) between 2010 and 2020.

New Application of Saligenyl Prodrugs Approach for the Delivery of Fosfoxacin Derivatives in Mycobacteria.

In this work, we implemented for the first time the Saligenyl prodrug strategy to increase the bioavailability of fosmidomycin phosphate analogs in bacteria. Here, we report the synthesis of 34 Saligenyl prodrugs of fosfoxacin and its derivatives. Among them, fifteen double prodrugs efficiently prevented the growth of the non-pathogenic, fast-growing .

In Vivo Sustained Release of the Retrograde Transport Inhibitor Retro-2.1 Formulated in a Thermosensitive Hydrogel.

A recently developed inhibitor of retrograde transport, namely Retro-2.1, proved to be a potent and broad-spectrum lead in vitro against intracellular pathogens, such as toxins, parasites, intracellular bacteria and viruses. To circumvent its low aqueous solubility, a formulation in poly(ethylene glycol)--poly(D,L)lactide micelle nanoparticles was developed.

Hijacking of the Enterobactin Pathway by a Synthetic Catechol Vector Designed for Oxazolidinone Antibiotic Delivery in .

Enterobactin (ENT) is a tris-catechol siderophore used to acquire iron by multiple bacterial species. These ENT-dependent iron uptake systems have often been considered as potential gates in the bacterial envelope through which one can shuttle antibiotics (Trojan horse strategy). In practice, siderophore analogues containing catechol moieties have shown promise as vectors to which antibiotics may be attached.

Identification of Dysregulated Expression of G Protein Coupled Receptors in Endocrine Tumors by Bioinformatics Analysis: Potential Drug Targets?

Background: Many studies link G protein-coupled receptors (GPCRs) to cancer. Some endocrine tumors are unresponsive to standard treatment and/or require long-term and poorly tolerated treatment. This study explored, by bioinformatics analysis, the tumoral profiling of the GPCR transcriptome to identify potential targets in these tumors aiming at drug repurposing.

Sex Bias in Differentiated Thyroid Cancer.

Differentiated thyroid cancers are more frequent in women than in men. These different frequencies may depend on differences in patient's behavior and in thyroid investigations. However, an impact on sexual hormones is likely, although this has been insufficiently elucidated.

How the Presence of Hemin Affects the Expression of the Different Iron Uptake Pathways in Cells.

Iron is an essential nutriment for almost all organisms, but this metal is poorly bioavailable. During infection, bacteria access iron from the host by importing either iron or heme. , a gram-negative pathogen, secretes two siderophores, pyoverdine (PVD) and pyochelin (PCH), to access iron and is also able to use many siderophores produced by other microorganisms (called xenosiderophores).

Dual Role of Thrombospondin-1 in Flow-Induced Remodeling.

(1) Background: Chronic increases in blood flow, as in cardiovascular diseases, induce outward arterial remodeling. Thrombospondin-1 (TSP-1) is known to interact with matrix proteins and immune cell-surface receptors, but its contribution to flow-mediated remodeling in the microcirculation remains unknown. (2) Methods: Mesenteric arteries were ligated in vivo to generate high- (HF) and normal-flow (NF) arteries in wild-type (WT) and TSP-1-deleted mice (TSP-1).

α,α-Difluorophosphonohydroxamic Acid Derivatives among the Best Antibacterial Fosmidomycin Analogues.

Three α,α-difluorophosphonate derivatives of fosmidomycin were synthesized from diethyl 1,1-difluorobut-3-enylphosphonate and were evaluated on . Two of them are among the best 1-deoxy-d-xylulose 5-phosphate reductoisomerase inhibitors, with IC in the nM range, much better than fosmidomycin, the reference compound. They also showed an enhanced antimicrobial activity against on Petri dishes in comparison with the corresponding phosphates and the non-fluorinated phosphonate.

Protective role of the mitochondrial fusion protein OPA1 in hypertension.

Hypertension is associated with excessive reactive oxygen species (ROS) production in vascular cells. Mitochondria undergo fusion and fission, a process playing a role in mitochondrial function. OPA1 is essential for mitochondrial fusion.

G Protein-coupled Receptors in Radioiodine-refractory Thyroid Cancer in the Era of Precision Medicine.

Context: Radioiodine-refractory thyroid cancers have poor outcomes and limited therapeutic options (tyrosine kinase inhibitors) due to transient efficacy and toxicity of treatments. Therefore, combinatorial treatments with new therapeutic approaches are needed. Many studies link G protein-coupled receptors (GPCRs) to cancer cell biology.

Pathophysiological adaptations of resistance arteries in rat offspring exposed in utero to maternal obesity is associated with sex-specific epigenetic alterations.

Background/objectives: Maternal obesity impacts vascular functions linked to metabolic disorders in offspring, leading to cardiovascular diseases during adulthood. Even if the relation between prenatal conditioning of cardiovascular diseases by maternal obesity and vascular function begins to be documented, little is known about resistance arteries. They are of particular interest because of their specific role in the regulation of local blood flow.

Phenotypic Adaptation of in the Presence of Siderophore-Antibiotic Conjugates during Epithelial Cell Infection.

Iron acquisition pathways have often been considered to be gateways for the uptake of antibiotics into bacteria. Bacteria excrete chelators, called siderophores, to access iron. Antibiotic molecules can be covalently attached to siderophores for their transport into pathogens during the iron-uptake process.

Somatostatin receptor ligands induce TSH deficiency in thyrotropin-secreting pituitary adenoma.

Objective: Somatostatin receptor ligands (SRL) are useful to control central hyperthyroidism in patients with thyrotropin-secreting pituitary adenoma (TSH pituitary adenoma). The aim of this study was to describe the frequency of thyrotropin deficiency (TSH deficiency) in patients with TSH pituitary adenoma treated by SRL.

Design: Retrospective study.

Human amniotic fluid-based exposure levels of phthalates and bisphenol A mixture reduce INSL3/RXFP2 signaling.

Background: The presence of chemical pollutants in the environment can affect human health. Epidemiological and in vivo experimental studies reveal reprotoxic effects (undescended testis) of phthalates (diethylhexyl phthalate (DEHP), dibutyl phthalate (DBP)) and bisphenol A (BPA), resulting in particular of a decrease in INSL3 (Insulin-Like 3 peptide) production. This hormone is essential for normal testis development and acts on a G protein-coupled receptor: RXFP2.

Functional dissection of the retrograde Shiga toxin trafficking inhibitor Retro-2.

The retrograde transport inhibitor Retro-2 has a protective effect on cells and in mice against Shiga-like toxins and ricin. Retro-2 causes toxin accumulation in early endosomes and relocalization of the Golgi SNARE protein syntaxin-5 to the endoplasmic reticulum. The molecular mechanisms by which this is achieved remain unknown.

Synthesis and biological evaluation of aryl phosphoramidate prodrugs of fosfoxacin and its derivatives.

Aryl phosphoramidate prodrugs of fosfoxacin derivatives 15a-b and 8a-b were synthesized and investigated for their ability to target bacteria. No growth inhibition was observed neither for Mycobacterium smegmatis nor for Escherichia coli on solid medium, demonstrating the absence of release of the active compounds in the bacterial cells. Investigation of the stability of the prodrugs and their multienzymatic cleavage in abiotic and biotic conditions showed that the use of aryl phosphoramidate prodrug approach to deliver non-nucleotides compounds is not obvious and might not be appropriate for an antimicrobial drug.

A Key Role for the Periplasmic PfeE Esterase in Iron Acquisition via the Siderophore Enterobactin in Pseudomonas aeruginosa.

Enterobactin (ENT) is a siderophore (iron-chelating compound) produced by Escherichia coli to gain access to iron, an indispensable nutrient for bacterial growth. ENT is used as an exosiderophore by Pseudomonas aeruginosa with transport of ferri-ENT across the outer membrane by the PfeA transporter. Next to the pfeA gene on the chromosome is localized a gene encoding for an esterase, PfeE, whose transcription is regulated, as for pfeA, by the presence of ENT in bacterial environment.

Thyrotropin receptor, still much to be learned from the patients.

In the absence of crystal available for the full-length thyrotropin receptor, knowledge of its structure and functioning has benefitted from the identification and characterization of mutations in patients with various thyroid dysfunctions. The characterization of activating mutations has contributed to the elaboration of a model involving the extracellular domain of the receptor as an inverse tethered agonist which, upon binding of the ligand, relieves the transmembrane domain from an inhibiting interaction and activates it. The models derived from comparisons with other receptors, enriched with the information provided by the study of mutations, have proven useful for the design of small-molecule agonists and antagonists that may be used in the future to treat thyroid dysfunctions.

Exposure to Maternal Diabetes Is Associated With Early Abnormal Vascular Structure in Offspring.

exposure to maternal diabetes increases the risk of developing hypertension and cardiovascular disorders during adulthood. We have previously shown that this is associated with changes in vascular tone in favor of a vasoconstrictor profile, which is involved in the development of hypertension. This excessive constrictor tone has also a strong impact on vascular structure.

In Vitro Effects of the Endocrine Disruptor p,p'-DDT on Human Follitropin Receptor.

Background: 1-chloro-4-[2,2,2-trichloro-1-(4-chlorophenyl)ethyl]benzene (p,p'-DDT) is a persistent environmental endocrine disruptor (ED). Several studies have shown an association between p,p'-DDT exposure and reproductive abnormalities.

Objectives: To investigate the putative effects of p,p'-DDT on the human follitropin receptor (FSHR) function.

Prolonged and Severe Gestational Thyrotoxicosis Due to Enhanced hCG Sensitivity of a Mutant Thyrotropin Receptor.

Context: Gestational thyrotoxicosis, whether associated with hyperemesis gravidarum or not, is thought to be due to excessive human chorionic gonadotropin (hCG) secretion.

Case Description: We report here the second case of gestational thyrotoxicosis associated with hyperemesis gravidarum due to a mutation of the TSH receptor, providing thyroid hypersensitivity to hCG.

Conclusion: Severe and lasting gestational thyrotoxicosis with normal hCG concentration should lead to sequencing of the TSH receptor gene.